The Building of Serapis forms an entity with the Terme dei Sette Sapienti and the Caseggiato del Serapide (III,X,2 and 3), and was built in the Hadrianic period. Shops flanking a vestibule open off Via della Foce. More shops are arranged around a courtyard with high arches. Two staircases led to upper floor apartments. Between two piers in the south-west part of the courtyard a cult-room (c. 2 x 2 m.) was built in the Severan period. In a niche in the back wall is a stucco relief of Serapis, sitting on a throne. On the side walls are paintings of Isis holding a sistrum, and of Isis-Fortuna with cornucopiae and rudder (yellow on a purple background). In the centre of the room is a brick altar. Next to the shrine is a passage to the Baths of the Seven Sages. It is decorated lavishly with a tympanum, and stucco reliefs of bucrania and garlands.

In a shop in the north-east part of the building a lime-kiln was installed at an unknown point in time (hence the modern name of the road to the east, Via della Calcara). Inside portraits were found of Trajan and Hadrian.