The nucleus of the epigraphic collection of the Museum consists of two collections from eighteenth-century Catania: that of the Benedictine monks of S. Nicolò l'Arena, and the collection of Ignazio Paternò Castello, Prince of Biscari. There are also some inscriptions from smaller local collections and from excavations in the nineteenth and twentieth centuries.

The collection of the Benedictine monks and the Prince of Biscari contain a variety of archaeological material and inscriptions. Most of this material comes from Sicily, and especially Catania, either from chance finds and excavations, or purchases, often from the antiquities market in Rome. Many ot these acquisitions were facilitated by the Benedictine prior Placido Scammacca, uncle of the Prince of Biscari.

It is due to Scammacca that the Christian epitaphs and the frescoes on display in this room came into museum, originally from the catacomb of Domitilla in Rome. Removed from different zones of the Roman cemetery, these frescoes were united in the collection of the Prince of Biscari in order to enrich his private museum. In a similar fashion, he brought together several inscriptions which include the Roman cognomen Paternus, to glorify the origins of his family, Paternò Castello.