He was the adoptive son of the condottiero Niccolò Piccinino and the brother of Jacopo Piccinino. At Niccolò's death (1444), he had been already established as a gallant warrior under the Duchy of Milan and the Papal States (1431). In 1436 he was serving the Aragonese Kings of Naples, taking part in the 1437 siege of Cerreto Umbra against Francesco Sforza but, after some successes, he left to besiege Assisi and then Pergola.