Set on the island of Crete across several decades of the 20th century, the novel follows four generations of the Petrakis family, whose lives are shaped by the leper colony on Spinalonga, a small island off the Cretan coast that housed Greece's quarantined leprosy patients until 1957.
The story opens with a brief prologue set in 1952. A young woman stumbles to a jetty in the coastal village of Plaka, leaning on her elderly father. He loads her into his small boat and ferries her across the water in a one-way journey to the colony. Her identity is not yet revealed.
The narrative shifts to 2001. Alexis, a 25-year-old Englishwoman, is holidaying in Crete with her boyfriend, Ed, growing disenchanted with both her career and their relationship. Her mother, Sofia Fielding, has always refused to discuss her Greek origins; the only clue is a faded wedding photograph of her Aunt Maria and Uncle Nikolaos on her bedside table. Before the trip, Alexis persuades Sofia to let her visit the village where Sofia grew up, and Sofia writes a letter of introduction to Fotini Davaras, an old friend still living in Plaka. Alexis drives alone to the village, explores the abandoned colony on Spinalonga, and meets Fotini at the local taverna. Fotini reveals that Alexis resembles "poor Anna," Sofia's mother, a name Alexis has never heard. Sofia's letter asks Fotini to tell Alexis everything, and over the following days, Fotini unfolds the entire Petrakis story.
In 1939, Eleni Petrakis, the beloved schoolteacher of the surrounding villages, discovers leprosy symptoms on her leg and departs for Spinalonga. She is accompanied by nine-year-old Dimitri, a pupil whose parents hid his diagnosis for over a year. Eleni's departure leaves her husband, Giorgis, a fisherman, to raise their two daughters alone: the volatile Anna, age 12, and the gentle Maria, age 10. On the island, Eleni transforms a dark house into a home and takes over the school. The colony is further revitalized when 23 leprosy patients arrive from an Athens hospital, among them Nikos Papadimitriou, a lawyer who becomes island leader and spearheads improvements to housing, water, electricity, and cultural life.
Dr. Nikolaos Kyritsis, a specialist from the Cretan capital of Iraklion involved in leprosy research, begins weekly visits to monitor patients, working alongside Dr. Christos Lapakis, the island's resident physician. When Germany invades Crete in 1941, the occupation brings starvation and brutal reprisals. Kyritsis's visits cease, and research is abandoned. Spinalonga remains untouched, as the Germans fear the disease. Eleni's condition worsens, and she dies when lesions close her throat. Giorgis breaks the news to his daughters; Anna is furious at not being warned, while Maria quietly comforts their father.
At the post-war celebrations, Anna, now nearly 18, catches the eye of Andreas Vandoulakis, son of the wealthiest landowning family in the region. After a formal courtship, they marry. Anna moves into the Vandoulakis world and all but disappears from Plaka, while Maria remains to care for Giorgis, learning herbal remedies from village elders. Four years into her marriage, Anna has not conceived, and life with the dependable Andreas has grown dull. When Manoli Vandoulakis, Andreas's charming and reckless cousin, returns after a decade abroad, Anna is drawn to him. Their flirtation intensifies, but Anna, realizing the danger, impulsively introduces Manoli to her unmarried sister. Manoli is captivated by Maria's unaffected beauty and begins courting her. After six months he proposes, and Giorgis joyfully consents.
Weeks before the wedding, Maria discovers a pale, numb patch of skin on her foot. She travels to Iraklion, where Kyritsis diagnoses leprosy. The engagement is broken. Manoli's reaction confirms that his feelings were shallow. Andreas's father, Alexandros, is furious to learn that Anna's mother also died of leprosy on Spinalonga and bans Giorgis from the estate. On a cold autumn morning, the scene from the prologue replays: Giorgis wraps Maria in a blanket and ferries her to the colony.
Maria settles into Spinalonga, transforming her house into a home, befriending Elpida Kontomaris, her mother's old friend, and practicing herbal remedies. Kyritsis resumes his visits and grows closer to Maria through regular conversations. Fotini crosses the water to visit Maria, bringing news from Plaka, including the troubling report that Manoli has resumed visiting Anna. Kyritsis begins a trial of dapsone, a sulfur-based drug, on selected patients. When a mob from surrounding villages descends on Plaka intent on destroying the colony, Kyritsis confronts the ringleaders on the quayside, threatening murder charges. The crowd disperses, and he realizes his courage came from his need to protect Maria. On the mainland, Anna gives birth to a daughter named Sofia, with Manoli serving as godfather and fueling speculation about the child's true paternity. Andreas gradually uncovers the affair.
After months of successful drug trials, patients begin testing free of the disease. A mass departure is planned for August 25, 1957. Maria and Lapakis are the last to leave the island, walking through the tunnel past abandoned houses and wilting geraniums. In Plaka, Kyritsis takes Maria aside and proposes. She says yes. That same evening, Andreas and Anna drive to the celebration. In the car, Andreas provokes Anna by suggesting Manoli might remarry Maria; her violent reaction confirms her obsessive love for Manoli. Andreas draws his pistol and shoots Anna. The gunshots are mistaken for fireworks. Kyritsis rushes to the scene but cannot save her. Andreas is arrested; Manoli disappears and is never seen again.
In the aftermath, Maria tells Kyritsis she cannot marry him, as she cannot abandon her bereaved father. Kyritsis accepts with grace: "And that's why I love you, Maria. Because you know what's right and then you do it" (421). Months later, when Lapakis vacates a hospital post in nearby Agios Nikolaos, Kyritsis secures the position and arrives unannounced at Maria's door to propose again. Maria accepts. They marry and settle in Agios Nikolaos. After Andreas's mother, Eleftheria Vandoulakis, dies of a stroke, Maria and Kyritsis adopt the young Sofia with the family's blessing.
On the night before 18-year-old Sofia leaves for university, Maria and Kyritsis reveal the truth: They are not her biological parents; her mother Anna was killed by her father Andreas; and Manoli may have been her real father. Devastated, Sofia flees to Athens and eventually marries Marcus Fielding, an English academic, telling him she is an orphan raised by an uncle and aunt. She resolves never to speak of her Cretan past. Kyritsis dies in 1990; Maria dies five years later. Sofia attends Maria's funeral overwhelmed with guilt but unable to make amends.
Back in 2001, Fotini urges Sofia to fly to Crete and tell Alexis the final chapter herself. At the taverna, Sofia describes her anger and her decades of guilt. Alexis insists the family story contains heroism as well as tragedy. The next morning, Alexis ends her relationship with Ed and catches a ferry, finding Sofia on deck. Alexis explains that hearing the family story made her realize she wanted a love as powerful as Maria and Kyritsis's. Sofia weeps freely, unburdened at last, and mother and daughter stand at the railings as the lights of Crete fade into the distance.