[1] He then attached himself to the service of Cardinal Ippolito de' Medici, and is supposed to have had some part in the unsuccessfil military expedition andertaken by Pope Clement VII against Siena, in 1526.

In 1527, he interested himself warmly for the imprisoned pontif, in whose behalf he composed five discourses addressed to the Emperor Charles V.[5] In 1532, he was sent by Cardinal Ippolito, in his own name, to Vienna.

[5] Tolomei was one of those to whom fellow Sienese, Bernardino Ochino, corresponded from exile in Geneva, where he had fled after abandoning his monastic position due to accusations of heresy.

A famous jurist and philologist, he wrote Lettere and Orazioni, which constituted a lively testimony of his participation in the literary disputes and political events of the time.

Tolomei was the defender of the Tuscan vulgate against the pure Florentineity of the language in the works of literary interest, anticipating many concepts of 19th-century scientific linguistics.