While still a student at the Collegio degli Ancarani, Sforza was created a cardinal deacon in the consistory of 18 December 1534 by Pope Paul III with the Deaconry of Santi Vito, Modesto e Crescenzia.

[2] The elevation to the cardinalate of his grandsons, Alessandro Farnese, aged fourteen, and Sforza, aged sixteen, displeased the reform party and drew a protest from the emperor, but this was forgiven when, shortly after, he introduced into the Sacred College Reginald Pole, Gasparo Contarini, Jacopo Sadoleto, and Giovanni Pietro Caraffa.

[3] In 1535, through Constanza's influence, his cousin Alessandro, gave up the position of administrator of the Diocese of Parma in favor of Guido Ascanio, who was also appointed papal legate of Bologna and Romagna.

This explains why Guido Ascanio and his brothers divided themselves, with considerable unscrupulousness, between the imperial and the French sides, maintaining in any case a marked family solidarity.

[4] He led the Spanish faction in the conclave held in December 1559, which resulted in the election of Pius IV who re-convoked the Council of Trent.