Under the first vault of the left aisle of the Cathedral is the marble entrance of the Libreria Piccolomini commissioned in 1492 by Cardinal Francesco Todeschini Piccolomini (Pope Pius III). The library was intended to house the extensive collection of books belonging to his maternal uncle Pope Pius II and to honor the memory.

It is a  large rectangular room well lighted and  with the walls and the ceiling entirely covered with ten (10) Pinturicchio 's splendid frescos whose colors are wonderfully preserved (1506 - 1507), illustrating the glorious events of the life of Enea Silvio Piccolomini, Pope Pius II.

 On the floor are are majolica tiles with the emblems of the Piccolomini family. The high altar is a grandiose work. Over the entrance door is a fin stucco bas-relief by Jacopo della Quercia. Other works by Sano di Pietro, Guidoccio Cozzarelli, Benvenuto di Giovanni, Michelangelo, Paolo di Giovanni, Jacopo della Quercia,  and Domenico Cafaggi