Mary Bishop showed up on the canvas in the spring of 2004. Mary was a grieving widow who had just lost her husband, Connor, whom she married in May 1998. Connor had been killed while serving as a soldier in the war in Iraq. She was still wallowing in her grief when a disoriented Nikolas Cassadine wandered onto her front porch. He had run his car off the road and then managed to walk to Mary's nearby cottage where he collapsed on the doorstep. Mary pulled him inside the cottage, and when he awoke, she told him that she was his wife! Nikolas had no previous memories of anything, including that of his current fiancée, Emily. Mary told Nikolas that his name was Connor Bishop, and he used to be a soldier in Iraq. Meanwhile, friends and family searched for Nikolas. Mary received a visit from Lucky Spencer, Nikolas' brother. Lucky was searching for Nikolas. Lucky had a photograph of Nikolas on hand and showed it to Mary. Mary lied and said that she hadn't seen that man in the photograph. In a desperate move, Mary took Nikolas' jacket and placed it by the river to throw off the search. Nikolas was presumed dead when the jacket was found near the river. When she returned to the cottage, Nikolas accused her of lying to him. Mary told Nikolas that he fled Iraq, and he was currently hiding out from the military police. Nikolas attempted to turn himself in, but Mary talked him out of doing so. Nikolas managed to sneak out of the cottage unseen and went to the riverbank in the hope that he would remember something. Little did he know that Emily was there as well. However, they didn't see each other.

Nikolas continually questioned Mary regarding his past and their past together. She desperately fed him pieces of the real Connor's past life, including that he had a talent for wood carving. Mary also worked hard at fending off Emily's search for Nikolas. Emily even came by the cabin a few times looking for Nikolas, unaware that he was just in the next room. Over time, Mary and Nikolas grew quite fond of one another. Mary also befriended Emily as they "bonded" over their grief for losing their loved ones.

When Nikolas' memorial service was held at a church near the cottage, Mary was in attendance. However, she didn't realize that Nikolas was also listening to Emily's eulogy from outside the church. Unfortunately, none of Emily's loving words triggered any memories for Nikolas. Mary was upset and scared to learn a little while later that Nikolas had taken the job to paint the church. But she ended up helping him paint the church. After a playful paint fight, they ended the day with some passionate kisses in the shower. But when Nikolas wanted to take things to the bedroom, Mary jumped out the shower. He found her sitting by the fire in the living room and demanded to know why she didn't want to be with him. She confessed that they were strangers to each other since he didn't remember her and she was afraid of losing him again. After a long talk, Mary gave in to her feelings and they headed for the bedroom. But a knock at the door interrupted them. It was Emily who wanted to talk and tell Mary about a job opening at the hospital. Mary tried to get rid of her, but it wasn't until Emily heard a noise from the bedroom that she left. Nikolas went flying out of the bedroom and wanted to know why she lied to Emily about his presence. Mary managed to calm him down by telling him that she only wanted to help Emily. Then they made love.

The next morning Mary was acting nervous around Nikolas, and he picked up on it. She told him that she didn't regret the previous night but had hoped that it might have awakened some memories for him. At the hospital, Mary ran into Emily who was cold towards her. After her interview, she saw Emily again. Emily apologized for being rude to her. She had judged her for being with another man so soon after the death of her husband but realized now that she had no right to do that. As Emily and Mary talked in the park, Nikolas happened by and listened in from behind some foliage. Later at the church, he told her about running into a parishioner that had given him a new perspective on his memory loss. Mary demanded to know if the stranger recognized him, but Nikolas said no and that he didn't think the guy would report him. She was also not happy to hear that he had gone into town for supplies. But she was glad to hear him tell her that he wanted to live in the present, and she believed that they could fall in love "all over again." Nikolas later proposed to Mary, who hesitated at first, but after he assured her he wasn't doing it out of guilt, she accepted.

Later, Mary discovered that the stranger who had seen Nikolas at the church was Lorenzo Alcazar. She was horrified to learn that Alcazar had offered Nikolas a job working for him. Mary tried to warn Nikolas off of associating with the dangerous mobster, and he agreed to think about it. Mary talked to Alcazar alone and Mary begged him to keep her secret. He agreed but informed her that Nikolas had accepted his job offer. Mary tried to talk Nikolas out of working for Alcazar but he was adamant about giving them a better life someday.

Nikolas rescued Emily after she crashed her car and brought her back to the cabin. Mary quickly made him hide and then tended to Emily. She called Jason, who was suspicious of Mary, to come get Emily. Emily later returned Alcazar's business card to her and warned her to stay away from the mobster. Mary later tried to get Nikolas away from Alcazar once again but failed. She later apologized for trying to keep Nikolas away from everyone else. Mary's fears about Nikolas working for Alcazar were realized when he came to their cabin bleeding from a gun shot wound. He had broken into the Quartermaine Mansion under Alcazar's orders and Emily had shot the "intruder," unaware that it was Nikolas. Panicked, Mary called Alcazar, who had one of his private doctors fix him up. Mary tried to threaten Alcazar into firing Nikolas by saying that she would expose Nikolas's true identity if he didn't. But Alcazar called her bluff by reminding her that he was helping her have the life she wanted. Alcazar offered to send the couple on a vacation so that Nikolas could recuperate. Mary thought Alcazar was working a private agenda, but Nikolas couldn't see how. Mary reluctantly agreed and Nikolas picked a spot in Mexico after being drawn to a brochure about it. The spot was the destination for a trip he had planned with Emily.

While in Mexico, Emily, who had convinced Lucky to go with her since Nikolas was "dead," was standing on the terrace when she looked over and discovered Nikolas standing on the terrace of his room as well. She's sickened when Mary comes out and kissed Nikolas. Emily later met Nikolas on the beach and she realized that he didn't know his real identity and didn't remember her at all. He begged her not to reveal that she had seen him and she reluctantly agrees. Mary and Nikolas had a great time in Mexico, unaware that Emily had discovered Mary's secret. But the honeymoon was over when Alcazar showed up with another job for Nikolas. Mary tried once again to get Nikolas to stop working for Alcazar but neither man wanted to end the partnership. Alcazar also warned her not to interfere in his business or he would reveal her secret.

Afraid of scaring Nikolas away from his loved ones just has Jason had been following his head injury, Emily waited to tell Nikolas about his true identity. She also dropped veiled hints to Mary that she knew. Mary struggled to justify to herself what she had done. Mary tried to persuade Nikolas against trying to regain his memory through hypnosis. But he was adamant and began to grow more confused over why the past she told him about didn't feel right to him. When Mary saw Nikolas and Emily happily talking to each other following one of his hypnotherapy sessions, Mary feared her secret was out. Despondent, she threw herself into the river. Alcazar found her and saved her. At the hospital, she asked him to find "Connor." Nikolas rushed to her side and promised not to try to regain his memory anymore as long as she was alright.

After she recovered, Nikolas asked Mary to quit working so they could spend more time together. Nikolas quickly grew frustrated with Mary and the supposed life they had shared. He demanded answers of her. She quickly offered to let him go, but he told her that's not what he wanted. Then she suggested they focus on the future by trying to have a baby. But Nikolas couldn't let his past go and asked Alcazar to run a background check on him. Alcazar told Mary about Nikolas's request. She gave him a dossier to give to Nikolas that painted Emily as a scorned former lover who wouldn't let go of "Connor." But Emily found out and finally told Mary she knew what Mary had been up to. Mary tried to defend her actions, but Emily screamed at her for befriending her and pretending to share her grief over losing Nikolas while secretly keeping Nikolas for herself.

Mary feared that Emily would run to Nikolas with the truth and felt that "Connor" was slipping away for good. So she took an overdose of sleeping pills. Nikolas came home and found her. As he revived her, she inadvertently called him Nikolas. Finally caught, Mary spilled to him what happened and tried to explain her reasons. But Nikolas didn't care and stormed out. Mary told Alcazar what had happened and Alcazar expressed his sympathies since he could tell that Mary loved Nikolas.

Mary remained hopeful that Nikolas would come back to her despite the fact he repeatedly told her that he would never be with her again. In an effort to move on, Mary went back to work at GH. She also annulled her marriage to Nikolas and told him she wanted to win him back as Nikolas and not "Connor." But he rebuffed her attempt to kiss him. Alcazar tried to help by telling Nikolas to take Mary with him and get Faith out of the country. But after Lucky came sniffing around, Alcazar called off the trip, much to Mary's disappointment. When Helena found out that Nikolas was alive, she tried to have him committed in order to gain control of his money. Mary offered to help him escape from Helena. But both Emily and Nikolas told Mary to stay away from them. Mary then ran into Helena, who offered to make Nikolas love her again if Mary helped her. Although tempted, Mary refused. However, when Helen found Nikolas and got him institutionalized, Emily blamed Mary.

Mary finally snapped and went after Emily for keeping "Connor" away from her. She hid in Emily's room, waiting for the opportunity to strike at Emily. But she also wandered around the house looking for her. She found and killed Sage Alcazar in the basement freezer and then later killed Trent with a gardening tool to the back in an upstairs hallway. She finally cornered Emily in her room and struggled with her over a butcher knife. As Emily struggled with the masked killer, she snatched the mask off to discover that Mary was her attacker. Nikolas vowed to kill her in front of Mac and everyone else in the house. In a showdown with Mac, Nikolas, and Emily, Mary told Nikolas that she had to kill Emily so they could have their life back. When Mary lunged for Emily, knife in hand, Nikolas grabbed Mac's gun and fired at her. The shot only wounded Mary, who was hospitalized. She had several visitors at the hospital, including Emily who told her that she wished she had died. Lorenzo came to see Mary as well, seeking revenge for Sage's death, but ended up not killing her. When Ric and Lucky tried to question her, she went into hysterics when they kept telling her that her husband was not Nikolas and that he was dead. Emily returned for another visit and warned her to stay away from Nikolas. Mary replied to Emily's warnings in the third person and told Emily that if Mary wasn't allowed a happy ending, then she would make sure Emily didn't have one either. After receiving her medication, Mary went into cardiac arrest and died. But the autopsy revealed she had been given the wrong medication and suspicion immediately fell on Emily. Emily had been alone with the medicine cart and had threatened Mary several times.