Dominick is a 41-year-old house painter living in Connecticut who serves as the lifelong caretaker for his twin brother, Thomas. Haunted by family history and personal losses, including the end of his marriage to his ex-wife Dessa, he carries deep-seated anger and struggles to cope with the heavy obligations placed upon him. Despite his gruff exterior and resentment toward his dysfunctional upbringing, he remains fiercely protective of his vulnerable brother.

Thomas is Dominick's identical twin brother who has lived with schizophrenia for over twenty years. He is gentle, highly sensitive, and heavily impacted by religious delusions and paranoia regarding government conspiracies. After performing a drastic act of self-mutilation to protest the Gulf War, he is involuntarily committed to a maximum-security ward, deteriorating rapidly under the strict confinement.

Concettina is the twins' recently deceased mother, a mild-mannered and deeply religious woman who harbored a special, protective bond with Thomas. She endured years of verbal and physical abuse from her husband, Ray, and maintained a profound, uncritical reverence for her immigrant father, Domenico. On her deathbed, she extracts a heavy promise from Dominick to always look after Thomas.

Ray is the twins' adoptive father, an emotionally distant man who adheres to an extreme, punishing version of traditional masculinity. During the boys' childhood, his attempts to "toughen up" the sensitive Thomas often escalated into physical and verbal abuse. In the present timeline, he lives a mostly solitary life, though his past actions continue to cast a long shadow over Dominick's emotional development.

Domenico is Dominick and Thomas's maternal grandfather, a Sicilian immigrant whom Concettina worshipped as an honorable, self-made man. His life story, revealed gradually through his translated manuscript, exposes him as an arrogant, power-hungry, and deeply flawed individual. His legacy shapes the family's generational trauma and forces Dominick to confront uncomfortable truths about his ancestry.

Dessa is Dominick's ex-wife, a resilient and compassionate woman who works hard to maintain independence from her wealthy family. She shares a long, complicated history with Dominick dating back to the summer of 1969, and their marriage eventually fractured under the weight of shared grief. She remains a supportive presence in Thomas's life despite her separation from Dominick.

Joy is Dominick's current live-in girlfriend, a lively but impulsive woman who is fifteen years his junior. She frequently expresses frustration over Dominick prioritizing his brother's needs above their relationship. Desperate for affection and stability, she struggles with her own past baggage and Dominick's emotional unavailability.

Dr. Patel is a psychiatrist assigned to evaluate Thomas at the maximum-security facility. Recognizing the interconnectedness of the twins' mental states, she begins providing therapy to a highly resistant Dominick. She uses audio recordings of Thomas to help Dominick unpack his repressed family history and lifelong resentment.

Lisa is Thomas's case manager at the maximum-security forensic institute. Initially appearing as a bureaucratic obstacle, she gradually becomes a sympathetic ally to Dominick in his fight to secure Thomas's release. She helps him navigate the complex, often indifferent mental health and legal systems.

Leo is Dominick's best friend since their teenage years and his former brother-in-law. Confident and sometimes self-serving, Leo operates with a brash charm that often contrasts with Dominick's brooding nature. They share a long history of adolescent misadventures, including a defining summer working for a city maintenance crew.

Ralph is a man of African American and Wequonnoc descent who grew up in poverty and faced intense discrimination in Three Rivers. He shares a complex, somewhat tense history with Dominick stemming from their school days and a shared summer job. In the present, he works at the hospital where Thomas is committed and acts as an inside source of information.

Nedra is a PhD student hired by Dominick to translate his grandfather's Italian memoir into English. She is erratic and unprofessional, eventually vanishing with the only copy of the handwritten text after a bizarre and confrontational evening at Dominick's home.

Angie is Dessa's younger sister and Leo's wife. Competitive with her older sister, she briefly dated Thomas during their younger years before marrying Leo following a sudden pregnancy.

Diogenes is Dessa and Angie's wealthy, status-conscious father. He owns a prominent local car dealership and has historically viewed Dominick as unworthy of his daughter, creating tension in Dominick and Dessa's early relationship.

Dell is a city public works supervisor who oversees Dominick, Thomas, Leo, and Ralph during a defining summer in their youth. He is an abrasive and mean-spirited boss who frequently targets Thomas with cruel teasing and bullying.

Ignazia is Domenico Tempesta's wife, a woman he essentially purchases through a reverse dowry after being dissatisfied with her older sister. Her life with Domenico in America is marked by misery, isolation, and constant mistreatment.

Prosperine is Ignazia's sister who moves to Connecticut to serve as Domenico's housekeeper. According to Domenico's memoir, she harbors dark secrets from her past in Italy and serves as a constant source of suspicion and tension in his household.

Thad is a friend of Joy's who spends time with her while Dominick is preoccupied with his brother's institutionalization. He is a frequent presence in Dominick's condo, causing friction between Dominick and Joy.

Henry is an elderly, eccentric man who has hired Dominick to paint his house. He grows increasingly impatient and demanding as Dominick's personal crises cause extreme delays in the project's completion.

Ruth is Henry's wife, who observes Dominick's erratic behavior as he attempts to complete the painting job on their house under extreme physical and emotional distress.

Penny Ann is Ralph Drinkwater's twin sister who suffered a tragic and violent death during their childhood. Her memory lingers in the town of Three Rivers and heavily impacts Ralph's trajectory in life.

Pasquale is Domenico's brother who travels with him to the United States. He works as a roofer and adopts a pet monkey, but his life in America is cut short by a tragic accident while helping Domenico build a house.

Vincenzo is Domenico's youngest brother. According to the memoir, his reckless behavior and sexual escapades ultimately lead to a fatal encounter with a police officer.