In 1492, the Archbishop of Siena, Cardinal Francesco Nanni Todeschini-Piccolomini (later Pope Pius III), founded the Piccolomini Library (Libreria Piccolomini) in the cathedral to store the most valuable family books and manuscripts with colorful miniatures from the collection of his uncle Enea Silvio Bartolomeo Piccolomini (Pope Pius II). The library room adjoins the left nave of the cathedral.
Inside the library are frescoes depicting ten significant events from the secular and religious life of Pope Pius II, first as a layman, then as a bishop, cardinal and finally as pope. Raphael also took part in the preparation of the paintings during his visit to Siena.