The palace, the first of Strada Nuova on the downstream side, was built by the architect Bernardo Spazio and the master Giovanni Pietro Orsolino commissioned by Pantaleo Spinola.

When the works were finished in 1564, the dwelling was inserted in the first list of the “rolli”, in 1576, in the first “bussolo”; passed to the Spinola of Tassarolo already in 1563 and, shortly after, to Andrea Spinola of the lords of Arquata, at least until its representation in the first edition of the collection that the Flemish Pietro Paolo Rubens dedicated to the Modern Palaces of Genoa, published in Antwerp in 1622.

Unlike the other buildings, the residence of Pantaleo Spinola faces Strada Nuova with a bare façade, simply plastered and without any decoration except for the portal, white marble, surmounted by statues of Prudence and Vigilance. The building underwent a major structural change during the third decade of the 17th century.

Other changes were completed in the second half of the seventeenth century. Passed into the property of the Giustiniani, the Cambiaso and then the Gambaro during the nineteenth century, the palace in 1823 became the property of a credit institution that made further changes.