Between 1565 and 1571 the Serbelloni family bought and demolished several houses on the site and originally built the palace in the baroque style.

[3][4] From 1679 the home hosted the governor of the State of Milan, Paolo Spinola, marquis de los Balbases, count of Melgar.

[5][6] The facade was remodelled in the neoclassical style between 1810 and 1814 by Innocente Domenico Giusti on the recommendation of city authorities and the Napoleonic viceroy as part of the renovation of the Corso di Porta Orientale.

[7] General Giovanni Francesco Arese (1642 – 1721) displayed his notable collection of paintings in the house, including works by Rubens, Titian, van Dyck, Ribera, Bronzino, Parmigianino, and Moroni.

[10] In this same period, the palazzo was home to Antonietta Fagnani Arese (1778–1847), the subject of Ugo Foscolo's ode "All'amica risanata."