During the reign of Pope Pius IV, Cardinal Farnese enjoyed good fortune. The Pope was a friend of his, and he was able to avoid the unpleasantries of international affairs, as he built a circle of friends in the College of Cardinals and in the Roman Curia. On 14 April 1564, Cardinal Farnese was promoted to the title of Cardinal Priest of S. Lorenzo in Damaso, a post he held for less than a month. On 12 May, he was promoted to the Order of Cardinal Bishops with the diocese of Sabina. He distanced himself from the horrors surrounding the fall of the Carafa nephews in 1561. Pius was not a healthy man, and his anticipated demise gave Farnese and others time to plan. Pope Pius IV (Medici) died on 4 December 1565.