Canon of Trento, Brixen and Salzburg, Cristoforo Madruzzo was elected bishop of Trento upon the death of Bernardo Cles in 1539. Later Pope Paolo III nominated him Cardinal on 7th January 1545. The figure of Cristoforo Madruzzo is undoubtedly linked to the Council of Trent (1545-1563).
He carried out many important diplomatic missions on behalf of Charles V and his son Philip II, which emphasised his great skills in diplomacy. He was also governor of Milan until 1558, when he returned to the Principality with the help of his nephew nominated coadjutor with right of succession given by the Pope in 1549. Madruzzo intensified his activity in Rome where he served at the Holy See, gradually moving aside for his nephew who was becoming more prestigious, to whom he eventually left the role of Prince-Bishop in 1567.