After studying law, he traveled to Rome and became a referendary of the Apostolic Signatura. On November 26, 1534, he became an auditor of the Roman Rota. He also became an auditor of the Apostolic Palace. With Latino Giovenale Manetti, he was sent as part of a diplomatic mission in 1535 to Charles V, Holy Roman Emperor and Francis I of France concerning ownership of the Camerino following the death of Giovanni Maria Varano, the last Duke of Camerino. From 1537 to February 1540, he was nuncio to the Republic of Venice. He was a protector of Ignatius of Loyola and the first Jesuits.
On August 20, 1540, he was elected Bishop of Bertinoro. On June 17, 1541, he was named nuncio to Ferdinand, King of the Romans, holding this position until 1545. On November 14, 1541, he was transferred to the see of Caserta. In August 1542, he traveled to Nuremberg with Otto Truchsess von Waldburg to present the Imperial Diet with the papal bull Initio nostri huius pontificatus (issued May 22, 1542) calling the Council of Trent, set to begin on November 1, 1542, and to attempt to convince German and Hungarian bishops to attend the council. He was promoted to the metropolitan see of Rossano on November 14, 1544. He was nuncio in Austria from February 1545 to 1547.
Pope Paul III made him a cardinal priest in the consistory of April 8, 1549. He received the red hat and the titular church of San Martino ai Monti on May 10, 1549. On November 9, 1549, he was transferred to the see of Capaccio.
He participated in the papal conclave of 1549-50 that elected Pope Julius III. He resigned the see of Rossano and Capaccio in favor of his brother, Paolo Emilio Verallo, in 1551. The new pope made him legate a latere to Henry II of France on September 9, 1551 to negotiate an end to the War of Parma between French troops and the Duchy of Parma. During this mission, he was accompanied by his relative Giambattista Castagna, future Pope Urban VII, who served as a datary. On September 18, 1551, Pope Julius III gave him the Palace of Sant'Apollinare alle Terme Neroniane-Alessandrine (though not the church property) ad vitam. From 1552 to 1553, he was Prefect of the Apostolic Signatura and a member of the Roman Inquisition. He opted for the titular church of San Marcello al Corso on November 29, 1553.