When Cesare returns to Rome, the city offers him a triumphant welcome. He regards his success against Savonarola as a turning point in his destiny.

Rodrigo has to rely on his secretary, Gacet, more than ever. In order to end Rodrigo's papacy, Della Rovere wants to procure a compromising document.

Under the influence of poison, Rodrigo suffers from hallucinations and embarrasses himself in public, so he elects to undergo withdrawal treatment.