The 1559 papal conclave was convened on the death of Pope Paul IV and elected Pope Pius IV as his successor. Due to interference from secular rulers and the cardinals' disregard for their supposed isolation from the outside world, it was the longest conclave of the 16th century.

Pope Pius IV, born Giovanni Angelo Medici, was head of the Catholic Church and ruler of the Papal States from 25 December 1559 to his death, in December 1565. Born in Milan, his family considered itself a branch of the House of Medici and used the same coat of arms. Although modern historians have found no proof of this connection, the Medici of Florence recognized the claims of the Medici of Milan in the early 16th century.