The film opens as Caravaggio dies from lead poisoning while in exile, with only his long-time, mute companion Jerusaleme by his side. Caravaggio thinks back to his life as a teenage street ruffian who hustles and paints, and is nurtured by Cardinal Francesco Maria del Monte, who catches the eye of young Caravaggio. As an adult, Caravaggio lives under the roof of del Monte, employing street people as models for his intense paintings. He is depicted as frequently brawling, gambling, getting drunk, and sleeping with both male and female models, including Ranuccio and Lena, who become embroiled in a murder plot involving Lena's death.
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