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Abstract:  The essay focuses on Diego Hurtado de Mendoza's years in Italy, ranging from the lively Venetian period to the stormy relations with the papacy in the years of the colloquies, from the Siena revolt to his recall to Spain by Charles V that effectively marked the end of his diplomatic carreer. Member of one of the most eminent Spanish families, Mendoza was ambassador for his country to Venice and Rome between 1539 and 1552. He was also a poet, a humanist. an avid collector of books and a discoverer of Greek and Arab codes. He his solid humanist culture, accompanied by eclecticism and a rare curiosity for the diverse, was nourished in Granada and in Italy, where he studied and was attracted by Pomponazzi's works. However, it was upon his upon his return to Italy as Charles V's representative that his culture flourished fully. The article examines Mendoza's distinctive anti-Papal and anti-curial policies in years when dialogue with the Lutherans was still open and the imperial Ghibellin dream of Charles V seemed still possible. It also looks into his fundamental role he in the cultural and religious history of the period. His political conduct and patronage attracted a microcosm that would shortly thereafter be cancelled by the orthodox shift of the 50s: artists, restless thinkers, all in search of an Italian path to the Reform.