Off the north aisle of the Duomo Nuovo, the Libreria Piccolomini is one of the cathedral's great treasures. Pope Pius III built this compact hall to house the books of his uncle, Enea Silvio Piccolomini, who became Pope Pius II; only a series of huge choral tomes remains on display.

The walls of the hall have vividly coloured narrative frescoes by Bernardino Pinturicchio. They depict events in the life of Piccolomini, starting from his early days as a secretary to an Italian bishop on a mission to Basle, through to his ordination as pope and eventually his death in Ancona while trying to mount a crusade against the Turks. In the centre of the hall is a group of statues known as the Tre Grazie (Three Graces), a 3rd-century Roman copy of an earlier Hellenistic work.