[1] In 1520, or as some say, 1525, Sigismondo renounced in his favour the See of Mantua; in 1527 his mother Isabella brought him back from Rome the insignia of the cardinalate.

He was chosen to be a cardinal at the very young age of 20, this quick ascention to power being the fruit of the diplomatic mastery of Isabella Gonzaga.

Like his friends Contarini, Gilberti, and Caraffa, he published a Latin catechism for the use of the priests of his diocese and built a diocesan seminary.

From 1540 to 1556 he was guardian to the young sons of his brother Federico II Gonzaga who had died, and in their name he governed the Duchy of Mantua.

[1] In 1561 Pope Pius IV named him papal legate to the Council of Trent, for which he had from the beginning laboured by every means at his command, moral and material.