Middlesex is a 2002 novel by Jeffrey Eugenides that tells a multigenerational, epic tale of a Greek family who immigrates to the US. The narrator, Calliope (or Cal) tells the story of how his grandparents, Lefty and Desdemona Stephanides, flee their homeland during a time of war and uncertainty, settling in the US. They harbor a family secret that changes the course of the narrator’s life: They’re brother and sister, and carry a genetic mutation that passes down to their son, Milton, and his wife, Tessie, who is Milton’s cousin. Tessie and Milton’s second child, Cal, is raised as a girl until adolescence, when it’s discovered that the child is male. Along the way, the family confronts forces of history, from wars and racial strife to the rising counterculture, as well as personal loss and the price of genetic inheritance. The book, which won the Pulitzer Prize for fiction, explores the US immigrant experience, the vagaries of love, and the importance of storytelling, while questioning conventional notions of sex and gender.

All quotations in this guide are from the 2002 Picador paperback edition.

Note: This guide uses Cal’s birth name and she/her pronouns when summarizing the early parts of his life, before his accident and subsequent decision to live as Cal. Afterward, Cal will be referred to by the appropriate name and pronouns. This is done to maintain consistency with the source text.

Content Warning: The novel contains outdated and offensive terms for both transgender and intersex people (such as “hermaphrodite”); depictions of nonconsensual medical interventions on intersex individuals; and descriptions of drug use.

Plot Summary

The narrator, Cal Stephanides, begins by informing his audience that he was born a girl. Although his grandmother’s silver spoon (unfailingly accurate in the past) predicts that he’ll be born a boy, his father insists that science trumps superstition. Milton and his wife, Tessie, calculate their coupling precisely to conceive a girl, and they do. Calliope Helen Stephanides is raised as the daughter they craved.

In Part 1, Cal traces the journey of his grandparents, Eleutherios (“Lefty”) and Desdemona Stephanides, from the Greek region of Turkey to Detroit, Michigan, in the US. After the Greco-Turkish War, Desdemona and Lefty are orphaned and eventually unhoused. Thus, they flee to the US in 1922, bringing with them Dr. Nishan Philobosian, whose entire family was slaughtered in the fighting; Desdemona’s silkworm box, which reminds her of home; and a deeply held secret: Lefty and Desdemona are brother and sister, a fact that they hide during their voyage to the US. On board the ship, they marry and consummate the union. The only person who knows their secret is their cousin, Sourmelina, who has her own secret—she’s a lesbian—and promises to keep theirs as well.

Lefty and Desdemona stay with Sourmelina and her husband, Jimmy Zizmo, as they adjust to living in a new country. Part 2 reveals how each approaches the assimilation process differently: While Desdemona longs for home, clinging to tradition and her Greek Orthodox faith, Lefty quickly acculturates, learning English and finding work. However, his assimilationist tendencies don’t protect him: Prejudice leads to his termination from the Ford Motor Company. Immigrants are viewed with suspicion; their foreignness is seen as a potential affront to American morality. Lefty ends up working with Jimmy, importing Canadian liquor—an illegal venture during Prohibition. Eventually, Lefty opens a speakeasy, the Zebra Room, where he spends much of his time, and he and Desdemona grow apart.

Their son, Milton, is the unwitting catalyst of the distance between them. When Desdemona is pregnant with him, Dr. Philobosian casually mentions that most birth defects are caused by consanguinity, or intermarriage. Desdemona fears that she and Lefty will be punished for their transgression, so she alienates herself from him. Although Milton shows no sign of ill health, Desdemona wants to avoid tempting fate by having more children. After becoming pregnant again and giving birth to their daughter, Zoe, she undergoes surgery to prevent future pregnancies.

Meanwhile, Milton grows up alongside his cousin Theodora, nicknamed Tessie, who is Sourmelina’s daughter. Shortly after Tessie’s birth, Jimmy dies (or so they think) in a bizarre car “accident”: He convinces himself that he’s not Tessie’s real father, that Sourmelina has been having an affair, possibly with Lefty, and drives his car over the thin ice of the river, falling into the icy waters below. Years later, he resurfaces as a minister for the Nation of Islam, only to be arrested for fraud. He leaves Detroit before his trial and is never seen again.

Desdemona is alarmed to learn that Milton is courting Tessie. Fearing that another illicit union might harm future generations, she sets Tessie up with Mike Antoniou, soon to be Father Mike. When Tessie accepts his marriage proposal, Milton, angry and heartbroken, joins the Navy to serve in World War II. As Tessie watches newsreels at the movie theaters, she realizes that she loves Milton and breaks off her engagement to Mike. Milton, however, has orders for the next shore incursion, a likely death sentence. He writes home, saying the letter will be his last. Desdemona agonizes. She tells Tessie she can marry Milton if he survives. Miraculously, he’s pulled back to the US to attend the Naval Academy, and the two wed. Father Mike later marries Milton’s sister, Zoe.

Part 3 sees the narrator’s birth, in January 1960. Calliope has a happy childhood. She’s close to her grandfather, who doesn’t talk. The night of her birth, Lefty has the first of several strokes; it leaves him unable to speak. Milton takes over the Zebra Room, turning it into a diner. Lefty, without much to do, resumes a gambling habit, losing everything. He and Desdemona must move in with their son and daughter-in-law. The Zebra Room declines as the city changes, and the politics of racial oppression explode into rioting during the late 1960s. The diner burns, and with the insurance money, the Stephanides move to the suburbs into the house they call Middlesex, after the street it’s on. Milton begins a new restaurant chain, Hercules Hot Dogs, that propels the family into the upper middle class.

As Calliope, nicknamed Callie, enters adolescence, her life becomes more complicated. Her parents enroll her in a private all-girls’ school, where the pecking order groups her with others labeled “Ethnic,” and she’s aware, for the first time, that she isn’t considered American in the same way as her white classmates. Also, while other girls begin to develop breasts and start their periods, Callie doesn’t. Instead, she has an unprecedented growth spurt, her voice deepens, and she begins to grow facial hair. Then, she falls in love with a girl she calls the Obscure Object. Her feelings confuse her for several reasons: She experiences typical adolescent angst at her own awkwardness, her physical development is uncharacteristic, and she feels the cultural pressure to conform to sexual mores of the time; in 1974, same-sex attraction still garnered much censure. The affair with the Obscure Object ends when the Object’s brother discovers them, and Callie runs away in distress. In doing so, she’s injured and is taken to the emergency room, where the doctors discover that Callie is, indeed, unique.

In Part 4, Callie is taken to a specialist in New York. After many physical examinations (some humiliating) and psychological questionnaires, Dr. Luce determines that Callie is chromosomally male but has a chromosomal abnormality that inhibited development of typical male genitalia. In puberty, Callie developed secondary sex characteristics associated with men as testosterone flooded her body. Since she has been raised as a girl, he suggests surgery to “correct” her physical expression, followed by hormone therapy. She can live comfortably as a woman for the rest of her life. However, Dr. Luce fails to mention that Callie’s unique biology or that the surgery will likely rob her of sexual sensation completely. When she discovers this, she runs away.

Hitchhiking to California, Callie becomes Cal, working in an adult club and displaying his unique genitals for paying audiences. The work is objectifying and difficult but allows Cal to come to terms with who he is and decide who he wants to be. However, when police raid the club, Cal has no option but to call his parents, after months away. When his brother answers the phone, Cal learns that his father, Milton, died in a car crash trying to retrieve fraudulent ransom money demanded by Father Mike, who (after years of frustration at being bested by Milton) pretended to have kidnapped Callie. While the loss devastates Cal, he considers that maybe it’s best that Milton doesn’t have to cope with his daughter’s transformation. Tessie will eventually accept him, and her love is undiminished.

Interspersed with the story of his family and how he came to be, Cal describes his current life as a cultural attaché in Berlin. He has never allowed himself to cultivate a lasting personal relationship and likes his peripatetic existence. However, he has been lonely. He meets another American expatriate, Julie Kikuchi, and the attraction is immediate and mutual. While it takes Cal a while to let down his guard, he knows that she’s worth the risk. He’s ready to tell his story.