Told in a segmented fashion, the film opens as Caravaggio (Nigel Terry) dies from lead poisoning while in exile, with only his long-time deaf-dumb companion Jerusaleme (Spencer Leigh (actor)) (who was given by his family to the artist as a boy) by his side. Caravaggio thinks back to his life as a teenage street ruffian (Dexter Fletcher) who hustles and paints. While taken ill and in the care of priests, young Caravaggio catches the eye of Cardinal Del Monte (Michael Gough). Del Monte nurtures Caravaggio's artistic and intellectual development but also appears to molest him.