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Gradoli was established in the Middle Ages around an imposing castle that is only accessible via a steep staircase that is said in Latin “gradus” and from which derives the name of the town.

Only a few traces remain of this castle such as a round defensive tower embedded in a private house, the entrance arch and part of the walls. The castle was sold by Matilde di Canossa to the papacy.

In the thirteenth century the town enjoyed a period of autonomy, then it came under the domination of various feudal lords until the second half of the fifteenth century when the Farnese came. It was first divided in half between the Farnese and Pope Eugenius IV, then from 1505 it passed in “perpetual parsonage” to the Farnese.

Cardinal Alessandro Farnese, later Pope Paul III, between 1517 and 1526, for the wedding of his son Pierluigi Farnese with Gerolama Orsini, commissioned Antonio da Sangallo the Younger to destroy the old castle and build a new mansion. The large building, finely painted, became the summer residence of Pope Paul III.

In 1537 it was included in the Duchy of Castro that Paul III had established for his son Pier Luigi.

Gradoli returned to the Holy See following the destruction of Castro and the end of the duchy in 1649.