<P> Izzie disapproves of George's relationship and marriage to orthopedic resident Callie Torres (Sara Ramirez). She and George sleep together, and attempt to keep their liaison a secret . George and resident Miranda Bailey (Chandra Wilson) are the only people aware that Izzie gave birth to a daughter at the age of sixteen; ultimately the child was given up for adoption . He supports Izzie when her daughter Hannah (Liv Hutchings), diagnosed with leukemia, arrives at Seattle Grace Hospital in need of a bone marrow transplant from Izzie . Izzie's feelings for George grow, and she reveals that she has fallen in love with him . When Callie discovers George has been unfaithful, the two separate, and George and Izzie embark on a short - lived relationship, only to discover there is no real chemistry between them . </P> <P> Izzie supports Alex when he discovers his new girlfriend has psychiatric problems, and convinces him to have her committed . She is also handed primary responsibility for the clinic, as Bailey cuts back on her responsibilities . Izzie and Alex go on to rekindle their relationship, though Izzie is concerned when she begins hallucinating Denny . She discovers she has metastatic melanoma (Stage IV) which has spread to her liver, skin, and brain, causing the hallucinations . Her survival chances are estimated at only 5% . She is admitted to Seattle Grace as a patient, and Derek Shepherd (Patrick Dempsey) successfully removes a tumor from her brain . Izzie spends her time in the hospital planning Meredith and Derek's wedding, but when her condition worsens and Derek discovers a second brain tumor, they give the ceremony to Izzie and Alex, who marry in front of all their friends . The procedure to remove the second tumor from Izzie's brain causes her to lose her short - term memory, and although she soon regains it, she flatlines moments later . The fifth season ends with her friends ignoring her DNR order and attempting to resuscitate her, transposed with images of Izzie in an elevator encountering George, who has been in an accident and is also currently flatlining . Though George dies, Izzie is resuscitated and recovers enough to return to work . </P> <P> Izzie makes a treatment error that endangers the life of a patient, and is fired from the hospital's surgical program . Believing Alex is partially to blame, she writes him a Dear John letter and leaves . Izzie later learns that Alex was not responsible for her lost job, and returns to make amends with him, but Meredith informs her that Alex is moving on . Izzie informs Alex that she no longer has cancer . Although he is pleased, Alex officially breaks up with Izzie, telling her that he loves her but deserves better . She leaves Seattle to start fresh . Several episodes later, Alex informs Meredith that Izzie sent divorce papers, which he signs in the episode "How Insensitive". In the sixth - season finale, Alex is shot and asks for Izzie . Imagining that Meredith's half - sister Lexie (Chyler Leigh) is Izzie, he apologizes and asks her never to leave him again . In the 300th episode, Alex reveals he never found out what happened to Izzie, but envisions a perfect, happy life for her, always smiling, now that he has moved on . </P> <P> Izzie was created by Grey's Anatomy producer Shonda Rhimes, with actress Katherine Heigl cast in the role . Heigl originally wanted to play Izzie as a brunette, but was requested to retain her natural blond for the part . Heigl's comprehension of medical procedures and terminology is slight; the actress explained that while she has an admiration for doctors, she is not as fascinated by medicine as other cast members . When Kate Walsh's character Addison Montgomery left Grey's Anatomy to launch the spin - off show Private Practice, Heigl disclosed that she had hoped for a spin - off for Izzie . </P>

What episode do alex and izzie get back together