When a young Roman inadvertently fell through a cleft in the Esquiline hillside at the end of the 15th century, he found himself in a strange cave or grotto filled with painted figures. Soon the young artists of Rome were having themselves let down on boards knotted to ropes to see for themselves. The Fourth Style frescoes that were uncovered then have faded now, but the effect of these freshly rediscovered grotesque decorations (Italian: grotteschi) was electrifying in the early Renaissance, which was just arriving in Rome.

When Raphael and Michelangelo crawled underground and were let down shafts to study them, the paintings were a revelation of the true world of antiquity. Beside the graffiti signatures of later tourists, like Casanova and the Marquis de Sade scratched into a fresco inches apart (British Archaeology June 1999), are the autographs of Domenico Ghirlandaio, Martin van Heemskerck, and Filippino Lippi.

It was even claimed that various classical artworks found at this time, such as the Laocoön and His Sons and Venus Callipyge, were found within or near the Domus's remains, though this is now accepted as unlikely (high quality artworks would have been removed to the Temple of Peace before the Domus was covered over with earth).

The frescoes' effect on Renaissance artists was instant and profound (it can be seen most obviously in Raphael's decoration for the loggias in the Vatican), and the white walls, delicate swags, and bands of frieze—framed reserves containing figures or landscapes—have returned at intervals ever since, notably in late 18th century Neoclassicism,[21] making Famulus one of the most influential painters in the history of art.