The palace is one of the most significant fifteenth-century residences in Reggio, commissioned by Francesco da Mosto, a high-ranking ducal official, who purchased it in 1472 and transformed it from a domus to a "palatium."

Of Ferrarese origin, it is attributed to the area of Biagio Rossetti (1488) and is now owned by the Manodori Foundation, which has recently restored it. After Francesco's death, the palace passed to other owners until in 1857 Pietro Manodori, then mayor of Reggio, acquired the palace from the Greppi counts of Milan to open a free nursery school open to all. Throughout the twentieth century, the structure was a laboratory for important pedagogical innovations capable of evolving to respond to ongoing social changes. The Manodori Nursery School remained open until 1991. Remarkable is the cornice with terracotta roundels of male heads. The staircase, which leads from the inner courtyard to the portico with arches that give access to the noble floor, was added in the eighteenth century to the original core and was originally adorned at the base with two stone dogs now preserved at the Palazzo dei Musei. In the basement, it is possible to see the pavements and levels of medieval dwellings. Inside, the ancient painted wooden coffers and traces of original painted decorations are preserved.