The silver reliquary is made in the form of a hexagonal temple decorated with enamelled plaques, depicting episodes from the life of St. Jerome. Two arms, joined to the sides of the shaft, serve as supports for angels: one holding the book of the vulgar Bible, which is the version translated into Latin by this saint, and the other his cardinal's hat.

The temple closes above in a segmented dome, and on this stands a statuette depicting San Girolamo, penitent.

The first information on the reliquary of San Girolamo is provided by its own inscriptions: from these we learn that the relics contained (an arm bone and the jaw) come from the substantial nucleus of sacred remains donated to the Cathedral by a certain Federigo di Chiaromonte, during the Council of 1439 and with the consent of Pope Eugene IV. Also reported is that creation of the reliquary is due to the canon Jacopo Manelli, who provided for the work in 1487. The maker’s mark of Antoni di Salvi, found in the brim of the Saint’s hat, confirms that this was the artisan commissioned for the work.