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

Of Ferrara origin, it is attributed to the area of Biagio Rossetti (1488) and is now owned by the Manodori Foundation which has recently restored it. Upon Francesco's death, the building passed to other owners until in 1857 Pietro Manodori, then mayor of Reggio, took over the building from the Greppi counts of Milan to open a free kindergarten open to all. Throughout the twentieth century, the structure was a laboratory of important pedagogical innovations capable of evolving to respond to the social changes underway. The Manodori kindergarten remained open until 1991. The cornice with round terracotta virile heads is noteworthy. The staircase, which leads from the internal courtyard to the arched loggia which leads to the main floor, was set against the primitive nucleus in the eighteenth century and was originally decorated at the base with two stone dogs now kept in the Palazzo dei Musei. In the basement it is possible to note the floors and levels of houses from the Middle Ages. Inside are the ancient painted wooden chests of drawers and traces of original pictorial decorations.