Around the middle of the 15th century, cardinal Ippolito II d'Este, the brother of the duke Ercole II,
chose it as his home in his natal city and he commissioned the modernization of the rooms of the Main Floor,
decorated with extraordinary grotesques.
When religious orders were partially disbanded following the unification of Italy,
in 1866 the building became State property. The nuns went back to their convent in 1872,
and the House was given to the Municipality of Ferrara to be used as a shelter for homeless families.
Because of the run down state of the building, the Municipality decided to demolish it in 1894.
However, the Italian Government intervened, purchasing Casa Romei and preventing its destruction.