This essay discusses Jeffrey Eugenides's novel Middlesex as a project in the American immigrant tradition, about the (self) making of its protagonist. The project is narrative (Callie/Cal is the narrator, even of things that happened before she/he was born), biological (Cal must negotiate the determinism of the DNA that gives him the condition of hermaphroditism), economic (the family fortunes sit precariously atop Detroit in the 1970s), racial (the immigrants “become white”), and cultural (she/he is Greek American). The novel uses new biological epistemologies to alleviate both anxiety about determinism and, paradoxically, anxiety about lack of clear identities, a tug of war that is of course intrinsic to American ethnic literature. Eugenides could be said to recoup the old American immigrant novel promising self-making within the political context of a city of race riots and a declining manufacturing economy. The new biology allows Cal to imagine his condition and his conditions of narration as those of plenitude (like those of Tiresias). He can narrate through his grandparents' and parents' mouths—literally make himself—as he recounts the night his parents conceived him. The “ancient Greek notion,” the old-world notion of “fate,” is akin to the racial determinism of the nineteenth century. The new genomic biology allows for excessive narrative and free will. Any analysis of the implications of Eugenides's narrative strategies should be as multifaceted and nuanced as the strategies themselves, particularly in light of other post-1990s developments in Asian American and African American literature. The renewal of the white immigrant saga in the era of the genome certainly bears both aesthetic and political analysis.