The palace was built in the 16th century on pre-existing buildings belonging to the Spinola family. It was named after Stefano De Mari, Doge of Genoa in 1663. The De Mari family was linked to Spain and Naples through business and trade.

It stands in the central section of what was the Vico Dritto, the main axis of the medieval road network that ran from Porta dei Vacca to the slopes of the Castello hill. The façade is organised by an illusive architecture that frames the windows on the different floors.

The monumental late 16th-century portal leads to an atrium restored in the 19th century in which there is a plaque commemorating an episode from the Risorgimento. The palace is organised around the luminous inner loggia courtyard, along which runs the staircase giving access to the various floors and private flats into which the building is now divided.

In one of the interiors one can still admire a fresco, attributed to Giovanni Battista Carlone and depicting Tobiolo and the Angel.