The following version of this book was used to create this study guide: Aciman, André. Enigma Variations. Farrar, Straus and Giroux, 2017. First edition.

Paul begins his story as a child on an island in Italy, where he lives with his father and mother. Through his father, Paul meets Nanni, a local cabinetmaker, with whom he quickly falls in love. Paul spends his days after school visiting Nanni, poorly concealing his crush. During this time, Paul moves into sexual maturity, masturbating to the thought of Nanni. Nanni never explicitly returns his affections, and she eventually asks Paul to stop coming. Paul is heartbroken. At 22, Paul returns to the island, allegedly to find out what happened to his family's property, but truly to find Nanni. Paul learns that Nanni has left the island, and learns that his father and Nanni were lovers.

Paul's narration then skips to him in his late 20s, living in NYC. Paul suspects his current partner, Maud, of cheating on him with another man. The couple attend a dinner party together during which Paul becomes increasingly sure that Maud is having an affair. Simultaneously, however, Paul imagines sleeping with another man at his tennis club. At the section's end, it is revealed Maud has not cheated on him, and the man in question was actually attracted to Paul.

The next section is dedicated entirely to Paul's attraction to the man at his tennis club, whose name is Manfred. Paul goes into explicit detail about his sexual attraction for Manfred, aligning Manfred with the divine. Throughout the section, Manfred never returns any of Paul's feeble advances. However, as the section ends, Manfred and Paul go out for a drink, where Paul confesses his love. Manfred returns Paul's affection, but the two do not do anything with their declarations.

Two or three years later, Paul and Manfred are a couple. Paul, however, keeps running into Chloe, his college crush. Having a long history, Paul and Chloe decide that they are "star lovers," which means they have a love that transcends time itself. Fearing that they will never truly be together (Chloe has a husband and Paul has Manfred), the two make a getaway trip back to their Alma Mater for one weekend. There, they decide their love is the only thing which will live past death, but ultimately decide they must return to their real lives.

A significant amount of time later, Paul tells the story of how he met Heidi, a young journalist. The two meet at Abingdon Square, have coffee, and discuss everything except each others' lives. Now an older man, Paul views Heidi as his last chance at true love, but Heidi rejects his advances. After Paul decides Heidi is truly not interested in him, he returns home, where the reader discovers Paul was married. This ending is bittersweet, for Paul does not achieve the relationship he desires with Heidi, but still has a quiet love for his wife.