Following the stories of two men castrated to ensure their perfect soprano voices, Cry to Heaven is a historical novel in 18th century Italy. Guido Maffeo is castrated at age six and enters the conservatory. He becomes a star until he loses his voice. When his voice is gone, he becomes a teacher, searching for a boy who can fulfill his lost dream. He comes to Venice and his life is intertwined with Tonio Treshi.

Tonio is the son of nobility and a beautiful singer. He dreams and talks of being a singer, but his family scoffs--that profession is for the castrati, not the son of a nobleman. Tonio's family is complicated, his mother a dark alcoholic who tips between lunacy and stupor, his brother (Carlo) reportedly disowned for seducing a common girl. But Tonio discovers the truth about his brother's sin and turns to his music to hide his fear and confusion. Tonio half-chooses and is half-forced into castration and begins a lifelong plot to take revenge on Carlo. He realizes at Guido's conservatory what has happened to him and refuses to sing. Guido is tormented by Tonio withholding his voice, but Tonio leaves the conservatory anyway.

Yet Tonio finds that he now has no place to belong and that his power is building. He returns and begins to sing. His two sides, dark revenge and heroic song battle for control. Tonio begins his journey of stardom and decadence, achieving no balance in his life. His sexuality proves to be a source of great complexity, confusion, and promise. The minute Tonio has sorted out his life and is finally happy, he hears his mother has died and his time has come to confront Carlo.