Due to the Italian Wars, the College of Cardinals was surrounded by three potentially hostile armies, loyal to Louis XII of France, Ferdinand II of Aragon, and Cesare Borgia (the cardinal-nephew and illegitimate son of Alexander VI).

A convergence of factors undid years of planning by Louis XII and his predecessor Charles VIII of France to promote the candidacy of Georges d'Amboise.

After receiving far fewer votes than expected on the first ballot due to the independent candidacy of Giuliano della Rovere and the loss of control of the Spanish cardinals by Cesare Borgia, d'Amboise threw his support to Cardinal Francesco Piccolomini, who was elected Pius III on the second ballot despite receiving only four on the first.

[2] Alexander VI had initially sided with Ferdinand of Aragon but in 1498 recognized Louis XII of France, the heir of Charles VIII, as the king of Naples.

[2] Rather than continue to Naples, Louis XII ordered his force to wait outside Rome for the duration of the conclave.

[1] The College of Cardinals initially decided to meet in Castel Sant'Angelo due to the triple threat of armed interference, and the start of the conclave was delayed by the need to prepare the building for this new use and for Cesare acquiesce to removing his troops from the city.

[6] His odds were set at 13 to 100, while della Rovere's were 15 to 100; Cardinal Piccolomini (elected Pope Pius III) was the favorite at 30 to 100.

[6] d'Amboise agreed to move the French army farther north as a sign of good faith before he realized the intentions of della Rovere.

[6] Furthermore, Cesare Borgia proved too ill to exert control over the Spanish cardinals, who instead followed the instructions of the king of Spain to vote against the French.