He was the son of Antonio Piccolomini, who had been granted the title Duke of Amalfi in 1461, for his services to king Ferdinand I of Naples.
[1] In 1497 he attended the coronation of King Frederick II of Naples in Capua.
In the following year he visited Abruzzi in order to assert his control over territory there.
He came into conflict with Carlo Sanframondi, the Count of Celano, who disputed Alfonso's rights in the area.
When he confronted the count in person at Solmona, their argument escalated into violence.