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In the present, Cal attends the opening of a Warhol exhibition at a museum in Berlin. He runs into Julie Kikuchi, who teases him for smoking cigars. They sit there smoking together, and Cal tells her that he needs to explain why he didn’t call her back.
Back in 1975, the mysterious man calls Milton back and claims to be holding Callie for ransom. He knows details of the Stephanides’ lives. He orders Milton to bring the ransom money to the train station. Milton leaves the house in the middle of the night. He doesn’t tell Tessie where he’s going because he knows she’ll tell him to call the police.
Milton arrives at the station and puts a briefcase with the money in a trash can as instructed. He almost leaves but decides to face the kidnapper. He finds Father Mike fishing the briefcase out of the trash. Father Mike scrambles to his car, and Milton runs to his Cadillac. Father Mike attempts to drive to Canada. Milton chases him, honking and screaming, trying to alert the customs agents. They order him to pull over, and Milton pretends to oblige but then speeds off after Father Mike across a bridge.
Cal imagines Father Mike feeling emasculated in his marriage to Zoë, shocked by going from church, where people treat him with deference, to his home, where Zoë treats him with ridicule.
Father Mike has to slam on his breaks when the car in front of him on the bridge stops. Milton’s car rams Father Mike’s, and Milton dies instantly.Cal, as narrator, imagines his father’s car sailing off the bridge instead. He imagines that Milton cries for the first time since childhood, upset at his failure to save Cal and thinking about how he had spent his life telling people the right way to do things, and now he has done something stupid.Cal says that perhaps it’s for the best that Milton never saw Chapter Eleven destroy Hercules Hot Dogs and never met the man Cal had become.
Cal explains to Julie Kikuchi that he’s always been interested in girls and that his intersexness has nothing to do with sexuality. She decides she’s okay with dating Cal. They go home and turn out the lights to have sex.
After the raid on Octopussy’s Garden, Chapter Eleven flies to San Francisco to retrieve Cal from jail. He finds the changes in Cal surprising but accepts him. Cal and Chapter Eleven fly home for Milton’s funeral.
When they reach the Middlesex house, Tessie stares teary-eyed at Cal. She had wanted a daughter so badly, and this doesn’t seem fair. Tessie asks why Cal didn’t want to stay the way he was. Cal explains that this is the way he was. Tessie eventually realizes that the change from Callie to Cal is not as dramatic as she’d feared.
Desdemona’s memory has faded, and she’s not well enough to go to the funeral. Cal takes Epsom salts to Desdemona to soak her feet. When Desdemona sees Cal, she mistakes him for Lefty. Cal explains that he’s her grandchild. Desdemona apologizes for not remembering him. Suddenly, Desdemona recognizes Cal as Calliope and asks what happened. Cal explains he grew up. Desdemona says she has heard of children in the village who look like girls and grow up to be boys. She blames herself, and Cal asks why. Desdemona explains that Lefty was her brother.
Cal wants to stay with Desdemona instead of going to the funeral, but Tessie objects. Cal starts imitating Milton’s hatred of the church’s expensive candles, which makes Tessie laugh. She agrees to let him stay because they both know Cal’s presence will be a distraction.
Desdemona proudly tells Cal that her spoon was right, and Cal agrees. She apologizes to Cal, but Cal assures her he’ll have a good life. He promises not to tell anyone that Desdemona and Lefty were siblings. She says that after she’s dead, he can tell everything. She later moves with Tessie and Zoë to New Smyrna Beach, Florida.
When few people attend the funeral, the family realizes that Milton had more business associates than friends. Back at the Middlesex house, Cal stands in the doorway, following Greek tradition to prevent Milton’s spirit from reentering. Cal doesn’t sense Milton’s spirit approach. He stands there, happy to be home, crying for his father, and wondering what he’ll do next.
Throughout the novel, Cal’s relationship with Julie has mirrored his journey of self-discovery that he writes about. In early chapters, Cal approaches Julie from a place of secrecy, which reflects the shame around sexuality he has learned from his family and his fear of rejection. He cuts off his relationship with Julie at the time in his narrative when Desdemona loses Lefty, matching his own loneliness to when Desdemona is left alone with her secret. Cal, as the physical consequence of Desdemona’s secret, cannot reveal his secret to Julie while Desdemona herself cannot speak it. In Chapters 27 and 28, Cal takes another chance with Julie at the same time as his past self finds acceptance and learns the origin of his mutation. These last glimpses of Julie, although not without conflict, show that Cal’s intersex body need not be the defining thing about him even within a romantic relationship. Even though Julie has a “normal” cisgender body, she still prefers to have sex in the dark, suggesting that she and Cal share a sense of modesty independent of Cal’s bodily worries. It also recalls the darkness in which Callie and the Object have sex, though, in this case, Julie is fully aware of Cal’s intersexuality, offering hope that Cal has found acceptance and desire from Julie.
In Chapters 27 and 28, Milton faces the consequences of cutting off his Greek heritage in pursuit of American acceptance. Milton’s worship of money and capitalism throughout the novel has alienated him from the larger Greek community and his own family. It is therefore significant that it is the reckless car chase for a suitcase of money, not really the pursuit of Callie’s kidnapper, that ultimately causes Milton’s death. Though Milton desperately wants his child back, it is his money he screams for as he chases Father Mike. His death therefore symbolizes the destructive nature of blindly pursuing money at the cost of all else. The lack of mourners at his funeral also highlights that his business, one of the signs of his success as an American, did not create lasting or meaningful friendships. In addition, Father Mike’s desire for vengeance initially stems from people telling him to be more like Milton, to whom he lost Tessie years ago. Himself associated with Greekness, femininity, spirituality, and poverty, Father Mike keeps hearing that Milton is associated with Americanness, masculinity, rationality, and wealth. He therefore concocts a scheme to steal some of that wealth. Although Milton would never break the law in such a way, it is nevertheless telling that Father Mike attempts to reassert his masculinity by pursuing money at the cost of his family relationships.
In Chapter 28, Cal embraces how, even living as a man, he deconstructs the gender binary. Tessie’s process of accepting Cal draws particular attention to the ways he blurs the boundaries between genders. Initially, Tessie wants a daughter because she feels outnumbered by boys in the house, and she believes women behave inherently differently from men. This belief comes in part from Tessie’s understanding of her role in the family as someone who upholds tradition, just as Desdemona does. Therefore, when she initially sees Cal, she feels betrayed because she believes she’s lost a companion in her role. However, as she sees when Cal lovingly but teasingly imitates Milton, Cal hasn’t actually changed because his personality isn’t tied to his gender expression. Instead of siding with the patriarch, he can still laugh at him with fondness just as he always did. In addition, Cal takes on Tessie’s role of tending to Desdemona and bringing her Epsom salts, a feminine role, but then transitions to taking the traditional male role of guarding the door to keep the deceased from returning. Cal has the freedom and flexibility to behave in a way authentic to him, blurring gender norms.
Cal’s powerful conversation with Desdemona brings him full circle, to the origin of his gene, allowing him to move forward and Desdemona to heal. Despite Desdemona’s failing memory, when she recognizes Cal as Callie, she reacts with confidence and understanding, not fear or anger. Because Desdemona recognizes and accepts Cal, she reassures him of his place in the family. Cal’s promise to Desdemona absolves her of the guilt of her incest because he reassures her that her sin has not doomed him to a terrible life, as she feared. Although it takes Cal years to fully embrace this promise, he does move forward, and we see him find closure by pursuing romance with Julie Kikuchi. Although Desdemona had been convinced she would die in Middlesex, after revealing her truth to Cal, she has the strength to move to New Smyrna Beach, where she had long ago wished to retire. No longer burdened by her secret, she is free to pursue her desires. At the very end of the novel, Cal, accepted by his family, participates in Greek tradition while keeping an eye on the future, symbolic of how returning home allows him to move forward.