Reporters and critics noted that many characters and events in Middlesex parallel those in Eugenides' life. The author denied writing the novel as an autobiography. In an interview by National Public Radio in 2002, he commented on the similarities:
|Because the story is so far from my own experience, I had to use a lot of details from my own life to ground it in reality, to make it believable for me and then hopefully for the reader, as well. So I would use my own physical appearance. I would use details from my grandparents' life, the streets they lived on, the kinds of places they lived. And all this made it real for me because it was a tall order to write such a story.|
Eugenides blended fact and fiction in his book. Like Cal, the author was born in 1960; he is not intersex, unlike his creation. His family moved to a house on Middlesex Road in Grosse Pointe, after the Detroit riot in 1967. Eugenides studied at University Liggett School, a private institution that served as a model for Callie's Baker and Inglis School for Girls. He tapped into his own "locker room trauma", an adolescent experience of being naked among many other nude bodies, and used it to develop Callie's self-discovery of her body during puberty. He based the name of the character the "Obscure Object" on a Brown University classmate whom he found alluring and to whom he gave that nickname.[note 5] Eugenides married a Japanese American artist, Karen Yamauchi,[note 6] and moved to Berlin.
Eugenides is also of Greek heritage, albeit only through his father's side. Although his paternal grandparents were not siblings like the Stephanides, they were of the same profession—silk farmers—as their fictional counterparts. Cal's learning of Greek customs to better understand his grandparents mirrored Eugenides' own actions to do likewise. The Zebra Room and the bartender profession are other items shared by their grandfathers; Eugenides said the inclusion of the bar was a deliberate "secret code of paying homage to my grandparents and my parents". Several aspects of Chapter Eleven were based on Eugenides' elder brother, who withdrew from society during a "hippie phase" in his life. While revising and editing the book, the author removed information that could be offensive to his relatives. Not all such material was excised, Eugenides said, "There may still be things in there that will sting."