The Treaty of Lyon ends the Italian War, confirming French domination of northern Italy, while Spain receives the Kingdom of Naples.

The Italian Wars of 1499–1504 are divided into two connected, but distinct, phases: the Second Italian War (1499–1501), sometimes known as Louis XII's Italian War, and the Third Italian War (1502–1504) or War over Naples. The first phase was fought for control of the Duchy of Milan by an alliance of Louis XII of France and the Republic of Venice against Ludovico Sforza, the second between Louis and Ferdinand II of Aragon for possession of the Kingdom of Naples.

The Kingdom of Naples, officially the Kingdom of Sicily, was a state that ruled the part of the Italian Peninsula south of the Papal States between 1282 and 1816. It was established by the War of the Sicilian Vespers (1282–1302). Until then, the island of Sicily and southern Italy had constituted the "Kingdom of Sicily". When the island of Sicily revolted and was conquered by the Crown of Aragon, it become a separate kingdom also called the Kingdom of Sicily. This left the Neapolitan mainland in the possession of Charles of Anjou who continued to use the name "Kingdom of Sicily". Later, two competing lines of the Angevin family competed for the Kingdom of Naples in the late 14th century, which resulted in the murder of Joanna I at the hands of her successor, Charles III of Naples. Charles' daughter Joanna II adopted King Alfonso V of Aragon as heir, who would then unite Naples into his Aragonese dominions in 1442.