The collection was brought together by Poldi Pezzoli (1822–1879) and his mother, a member of the Trivulsi family. Poldi Pezzoli bequeathed the house and collection to the Brera Academy, who in 1881, opened the museum.

The palace in built in Neoclassical style by the architect Simone Cantoni (1736–1818), whereas the interior was redecorated in the 19th century.

During WW II the palace was heavily damaged, but restored and re-opened in 1951.

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