Colleen was introduced through a series of flashbacks during the summer of 2007. Her story was part of the Brady/DiMera feud genesis reveal.
Years earlier, Colleen was a novice living in Ireland. She was studying to become a nun, but had not taken her final vows yet. She met Santo DiMera when he came into the church with an injury. Colleen nursed him back to health. He immediately was drawn to her and started courting her. Initially, she rejected his advances, but slowly she started allowing her brother, Shawn, to spend time with Santo's son, Stefano, which meant that Colleen spent time with Santo. Santo told Colleen that his wife had died. Santo eventually proposed marriage and Colleen accepted. But, when Colleen's father found out that she was leaving the church, he threatened to disown her. Colleen was still determined to marry Santo. But then, Shawn told Colleen that he learned from Stefano that Santo's wife was still alive and living in Italy. Colleen was crushed and left Santo. Determined to make amends with her family, Colleen took her final vows to become a nun. But Santo appeared during the ceremony to make one last plea for Colleen. She ran out of the church, to a cliff side, and left her habit on the top of the cliff. No one heard from her for years. Her family and a heartbroken Santo assumed that she was dead.
Colleen was not dead. But, she was pregnant. She fled to Argentina to get away from Santo and to save her family from the embarrassment of the stigma that bearing a child out of wedlock would bring at the time. In Argentina, she gave birth to a baby boy and named him Ryan. She found work as a seamstress, but she could not make enough money to support herself and Ryan. So, she found an orphanage that would take Ryan and allow her to visit on the weekends. One weekend, she came to visit, and Ryan was gone. He'd been adopted by the Alamain family. Convinced that he would have a better life without her, Colleen did not try to contact Ryan. She continued her work as a seamstress and eventually parlayed those skills into a career as a fashion designer of sorts, for the middle- and lower-class working families.
Decades later, an elderly Colleen learned that Stefano DiMera had blamed her for his miserable childhood. Apparently, after Colleen ran away, Santo became an angry and vindictive father. Stefano tortured the Bradys in retaliation. Colleen set out to save her family, starting with her immediate family first. She could not risk contacting her family because she was not sure if Stefano knew that she was still alive. So, she sent people to kidnap her great-granddaughter Claire. When Claire disappeared, Shawn, Belle, Bo, Hope, Philip, and Chloe all traveled to Ireland to search for Claire. John, Marlena, Steve, Kayla, and Grandpa Shawn traveled to Ireland, as well. Once there, they all met Colleen and learned the truth about her life: her affair with Santo, her "fake" death, and her long-lost son, who grew up and was believed to be living under the name John Black.
John, who was recovering from being brainwashed by Stefano, was shocked to learn that Colleen was his mother, but he was even more shocked to learn that Stefano had programmed John to kill Colleen. John went to Ireland with the intent of carrying out his assassination mission. But, he could not find it in himself to kill his own mother. Colleen died a few days later, of natural causes, surrounded by her friends and family.
Colleen's ghost reappeared occasionally, usually to Sami. Sami and Colleen had an identical resemblance (as did E.J. and Santo) and the show often showed Colleen as a figment of Sami's imagination.
In 2013, John contacted the orphanage to get more information about his past. They confessed that they had lied to Colleen Brady because they couldn't bring themselves to tell her that her son had died. John was not the child of Colleen and Santo.