The House of Pico della Mirandola were a noble family first known for one Hugh, a vassal of Matilda of Tuscany in the 11th century.

In the following centuries, members of the family were podestà in Modena and Reggio Emilia, until, in 1311, Francesco Pico received from Emperor Henry VII the fiefs of Quarantoli and San Possidonio in reward of his help during the war against the Este.

The main economic activities in Renaissance times were animal husbandry, agriculture and, starting from the 17th century, silk clothes.

The duchy however suffered from internal crisis and the numerous military operations in the area, such as in 1630 when it was ravaged by the imperial troops.

The last lord was Francesco Maria Pico, who was charged with treason after having been forced to cede the fortress to the French.