The palace was built for Ambrogio Di Negro, several times magistrate, governor and ambassador for the aristocratic Genoese Republic until he became doge in 1585-1587. Ambrogio himself also proved his culture through the creation of the magnificent villa with garden, today known as Villa Rosazza allo Scoglietto, admired by foreign visitors until the end of the 19th century.

It was built on previous medieval buildings and shares the architectural innovations of the contemporary Strada Nuova palaces. It was built in an urban area of outstanding importance, an ancient market place immediately behind the port and crossroads of important urban routes.

The palace overlooks one side of this urban space with two main facades decorated with frescoes, on a high ashlar basement, including the ground and mezzanine floors destined for shops, according to the noble Bramante model already experimented by Cipriano Pallavicini in the Fossatello Palace.

The interior spaces of the first piano nobile are a clear expression of the extensive humanistic culture of the commissioners, who had frescoes depicting subjects from mythological tales accompanied by Latin mottos such as "Danae impregnated by Zeus in the form of a golden shower", "the Myth of Perseus and the Rape of Helen" by Andrea Semino, in the vaults of the salons and drawing rooms.

In the great salon, marked by the presence of interesting black stone portals, there are clear reminders of overcoming adversities, possibly an allusion to the rivalry between 'old nobles' and 'new nobles'.