On 17 June 1537, Farnese was appointed Administrator of the Diocese of Bitonto in the Kingdom of Naples on the resignation of Bishop Lopez de Alarcon; his administration ceased upon the appointment of a new bishop on 8 January 1538. He became Administrator of the Diocese of Massa Marittima on 15 November 1538, on the resignation of Bishop Hieronymus de Glanderonibus; since he was only eighteen, he was not canonically eligible to be the bishop, though he could—and did—collect the income of the bishop until a successor was appointed in April 1547. On 16 July 1540, Farnese was named Administrator of the Diocese of Cavaillon in Provence, which he resigned one year later on 20 July 1541. In 1549, his grandfather Pope Paul III died.