Beneath the presbytery of the Cathedral, since the Romanesque origins of the building, there is a crypt, also divided into three naves and accessed via a steep side staircase. Following its collapse in 1606, it was definitively rebuilt in 1614, coinciding with the transfer of the relics of the city's most venerated saints, among whom Sant'Omobono, canonised in 1199 and patron saint of the city, is particularly noteworthy. 

Among the most important works housed in the crypt are fragments of a mosaic decoration dating back to the early 12th century and the famous ark of Saints Marcellino and Pietro, formerly in San Tommaso and later moved to the crypt of the Cathedral. Its construction, which dates back to the early 16th century, was initially attributed to Benedetto Briosco, a sculptor working at the Certosa di Pavia, but its current appearance is due to the work carried out in 1609 by Matteo Galletti, who recomposed the ark using pieces made by Briosco, some newly made decorations and a panel depicting Ecce Homo by Giovanni Antonio Amadeo from the Ark of Sant'Arealdo.