San Silvestro in Capite
Pope Julius III made him a cardinal priest in the consistory of November 20, 1551. He received the red hat and the titular church of San Silvestro in Capite on December 4, 1551. Shortly thereafter, he became Prefect of the Apostolic Signatura. On August 13, 1552, the pope made him legate "a latere" to pacify Siena. On May 17, 1553, he resigned the government of his diocese, becoming administrator of Grosseto; he resigned in favor of his nephew, Giacomo Mignanelli on October 2, 1553. Pope Julius III then made him Prefect of the Papal States.