The patron saints of Velletri are Saint Clement and Saints Annia and Gerontia, virgins and martyrs, celebrated on 23 November. The cathedral basilica of San Clemente, an ancient Roman basilica known since the 5th century, was later converted into a Christian church: the building, with an apse and three naves supported by masonry pillars, holds the precious, very old icon of the Madonna delle Grazie. Pope Alexander IV, previously bishop of Velletri, ordered during his pontificate (1254-1261) that the relics of the martyr saints Pontian and Eleutherius be transferred to the town, kept ever since in the crypt beneath the cathedral.
The diocese of Velletri gained growing importance between the 5th and 6th centuries, when in 592 Pope Gregory I merged into it the declining diocese of Tres Tabernae, on the Appian Way. The cathedral's cloister today houses the Diocesan Museum, which gathers works of inestimable value including the Crux Veliterna, a precious 11th-12th-century reliquary in filigree gold and enamel, and paintings by Gentile da Fabriano, Antoniazzo Romano and Sebastiano Conca. In 1589 Pope Sixtus V separated the town's civil government from the bishop's temporal power, restoring freedom to the commune, only to see the two powers reunified in 1591 at the will of Pope Gregory XIV.
