It was built from 1562 for Baldassarre Lomellini, banker to King Philip II of Spain, to a design by Giovanni Ponzello, «chamber architect» of Genoa and designer of Palazzo Tursi, belonging to Niccolò Grimaldi, Baldassarre's son-in-law.

Of the original 16th-century façade, only the white marble portal by Taddeo Carlone survives today, bearing the inscription 'venturi non immemor aevi'.

[2] The intervention, carried out starting in 1773, led to the creation of the sober and rigorous atrium, the porticoed courtyard that replaced the original garden, and the terrace above, adorned with classical-style pavilions.

After a decade of work, which led to the extension of the west wing and a renewed interior decoration in the French taste, Spinola, having moved to France, sold the building to Marquis Domenico Serra.

In 1917 it was then purchased by the shipowner Tito Campanella, who established his offices there and lived on the second piano nobile.