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While Alexander worries that Juan has not come home, Savonarola is tortured on the rack but will not confess. Cesare, determined to destroy his legacy as well as his body, fakes a confession and Savonarola is burned as a heretic.
Meanwhile, a new suitor for Lucrezia’s hand – Alfonso of Aragon – arrives in Rome. Playful Lucrezia sets out to play the minx with him as with the others, then surprises herself by falling for him. She announces she will marry him. The Pope’s joy, however, is short-lived when he receives dire news, furthered by a shocking confession from Cesare.
Later, during celebrations for Lucrezia’s betrothal, Alexander and Cesare reunite over a cup of wine, but Antonello is there and Cesare realizes the danger too late as the Pope raises the poisoned cup to his lips.