Cesare's diplomatic mission is a success; Bianca takes her own life; Alexander and Sforza conspire to repay Gonzaga; Lucrezia travels to Naples; King Ferdinand continues the refusal of recognizing Giovanni.

Cesare burns Constanzo's palace to contain the plague; Lucrezia seeks a Neapolitan power base for herself; one of the candidates for Ferdinand's replacement is accused of trying to kill the other.