Designed around the year 1300 as a replacement for the earlier Romanesque cathedral, building work continued until the end of the following century. The incomplete façade, which gives on to Piazza Dante, is characterised by a baroque portal by Pietro Carattoli (1729). The side which gives on to the fountain, also incomplete, features a portal by Galeazzo Alessi built in 1568, a precious 15th century pulpit and a wooden crucifix by Polidoro Ciburri, placed here during the salt war (1540). The interior, with its characteristic structure, was totally rebuilt and decorated in the 1700s. The chapel of San Bernardino preserves the Deposizione by Federico Barocci (1569).

In the chapel of San Giuseppe is the chiselled reliquary of the Santo Anello (or Madonna’s wedding ring) as well as Wicar’s copy of Perugino’s Sposalizio di Maria, stolen by the French during the Napoleonic period. The windows were made in Perugia in the renowned laboratory of Morettini-Caselli. In the apse is a wooden choir by Giuliano da Maiano and Domenico del Tasso (1491), which was restored after a fire in 1985. The sacristy housesa cycle of paintings of the Martirio di San Lorenzo by Giovanni Antonio Pandolfi (1573-76).