The House of Piccolomini is the name of an Italian noble family, Patricians of Siena, who were prominent from the beginning of the 13th century until the 18th century. The family achieved the recognized titles of Pope of the Catholic Church, Prince of the Holy Roman Empire, Grandee of Spain, and Duke of Amalfi. The family is also featured in Florentine Histories, a book written by Niccolò Machiavelli, where he describes the reign of Pope Pius II, who had allied himself with the Venetians and Prince Vlad Dracula, to wage a war against the Sultan of the Ottoman empire.

Pope Pius II, born Enea Silvio Bartolomeo Piccolomini, was head of the Catholic Church and ruler of the Papal States from 19 August 1458 to his death.