In 1503, the now-frail Francesco, known as Cardinal Piccolomini, was elected pope as a compromise candidate between the Borgia and della Rovere factions.

Francesco was received as a boy into the household of Aeneas Silvius who permitted him to assume the name and arms of the Piccolomini family.

In the excited tumult following the announcement, the Roman mob sacked his house, which was located near the church of S. Agostino, not far from the north end of the Piazza Navona; even the marble stones were taken.

In 1476, Cardinal Francesco deeded the palace to his brothers Giacomo and Andrea, and their descendants, on the condition that it not be alienated from the male line.

The Palazzo Piccolomini no longer survives, having been razed to make room for the new church of Sant'Andrea della Valle, which was begun in 1591.

[20] On 26 March 1463, Pope Pius II granted Cardinal Francesco the monastery of San Saba on the Aventine Hill in commendam.

[35] He was named the administrator of the diocese of Pienza and Montalcino on 31 October 1495, and occupied it until 14 March 1498, when he resigned in favor of his relative, Girolamo Piccolomini.

[36] Following the murder of his son Giovanni Borgia in 1497, Alexander VI appointed Francesco Piccolomini a member of a commission of six cardinals, in a short-lived effort to reform the Roman Curia.

[37] On 8 February 1501, Pope Alexander also appointed Piccolomini, in his capacity as Protodeacon, to a commission to take charge of the income from the tithe (decuma), and dispensing it for yet another contemplated crusade against the Turks.

Francesco commissioned the artist Pinturicchio to fresco its vault and ten narrative panels along the walls, depicting scenes from the life of Pope Pius II.

Its iconography illustrating the donor's career gives an edited version of Pius II's life, passing over his former support of the Antipope Felix V. Though Pinturicchio labored for five years, the books never reached their splendid destination;[further explanation needed] yet the Piccolomini Library is a monument of the High Renaissance in Siena.

[citation needed] Pope Alexander VI died on 18 August 1503,[39] and amid the disturbances consequent upon his death, it took the combined pressures of all the ambassadors in Rome to induce Cesare Borgia to withdraw from the city, so that an unpressured conclave might take place.

Despite urgent pleas of the cardinals to stay away, both the Orsini and the Colonna factions entered the city with troops, intending to avenge old and new grievances.

[42] This selection can be seen as a compromise between factions, Borgia and della Rovere, picking a frail cardinal with long experience in the Roman Curia over the kin of either Sixtus IV or Alexander VI.

Normally, a pope did not hold such meetings until after his coronation, but Pius III was faced with an emergency, and he was being hard pressed by the Spanish cardinals.

[43] A French army, which was nominally under the command of Cesare Borgia, who was ill and in bed, was demanding passage through Rome in order to attack the Spanish government in Naples.

The next day, he told the Venetian ambassador, Antonio Giustinian: "In consequence of the pressure put upon me by the Spanish cardinals, I have been compelled to some briefs in favour of Cesare Borgia, but I will not give him any further help.

"[45] On the morning of 26 September, the newly elected pope underwent an operation on his ulcerous left leg, enduring the pain of cutting in two places.

[52] Some have alleged that Pope Pius died of poison administered at the instigation of Pandolfo Petrucci, the ruler of Siena.

[54] When the basilica was being rebuilt, the monument was transferred below to the grottoes and the remains of Pius III and his uncle to the church of San Andrea della Valle in Rome put in a mausoleum created by Cardinal Alessandro Peretti di Montalto in 1614.