We Greeks get married in circles, to impress upon ourselves the essential matrimonial facts: that to be happy you have to find variety in repetition; that to go forward you have to come back where you began.

Cal says this in Chapter 4 during Desdemona and Lefty’s wedding. This quotation introduces the idea that patterns within Desdemona and Lefty’s relationship will resurface throughout their lives and in new generations. Time in Middlesex has a circular nature, with new events often echoing previous ones. Although Tessie and Milton are not siblings, they are related, echoing Lefty and Desdemona’s incest. Life or death situations precipitate the marriages of both Desdemona and Lefty and Tessie and Milton. The cyclical nature of time ties into the theme of genetic destiny because it expands the idea of inheritance to patterns of behavior, not just biological phenomena. For Cal, who physically carries the consequences of these past cycles, these patterns offer little comfort at first because they appear to doom him to loneliness. However, by the end of the novel, seeing himself in his family members also reassures him that he belongs to his family, even if he is different.

The second part of the quotation about having to return in order to go forward plays out in the novel both literally and figuratively. When Milton achieves a significant marker of the American dream, moving to a house in Grosse Pointe, Lefty’s dementia causes him to mentally travel back to the village, representing the full cycle of immigration. After leaving San Francisco, Cal’s return to Grosse Pointe gives him the opportunity to learn the origin of his mutation from Desdemona, starting a process of healing. He continues this process by writing his memoir, in which he seeks to move forward in his life by examining all the elements of his ancestry and reconciling with them. New beginnings often pair with shocking or violent losses, as when Zizmo disappears the day Milton is born. New generations come with the passing of the old.