The building was again renovated in the mid-16th century by order of Andrea Doria, who commissioned the work to Giovanni Angelo Montorsoli (changes included the presbytery and the dome).

The façade includes a late Roman sarcophagus with an Allegory of the Autumn, which originally was used as the tomb of Lamba Doria, who had taken it to Genoa from Korčula in Dalmatia.

At one time, large chains, which once had protected the harbor of Pisa and which had been obtained as booty after the victory at the Battle of Meloria (1284), were draped across the facade.

Artworks of the interior include the Miracle of the Ethiopian Dragon by Luca Cambiaso and the Vocation of St. Matthew by Giovanni Battista Castello, a wooden "Deposition" by Anton Maria Maragliano, and the tomb of Andrea Doria, executed by Montorsoli, in the crypt.

According to the tradition, the sword housed under the altar belonged to Andrea Doria, and was donated to this church by Pope Paul III.