Remarkably few documents concerning the early life of Bendinello Sauli have survived. The first member of the second branch of the family to be dedicated to a career in the Church, he was probably born in about 1481, the eldest of the five sons of Pasquale Sauli quondam Bendinelli and Mariola Giustiniani Longhi quondam Giacomi, a member of the largest Genoese popolare family (see Fig. 2). As the eldest son, he would normally have been expected to carry on the family business and there is evidence that his early years were spent in learning to do just that. On 14 July 1492 a very young Bendinello was in Rome to help deliver cloths to the camera apostolica on behalf of Paolo Sauli for the appalto degli spirituali and on 1 December 1499, having availed himself of the venia aetatis and thus declaring himself to be legally competent and an adult over the age of fourteen, he acted on behalf of himself and his brothers to arrange the rental of a property below their house near the Porta Sant'Andrea in Genoa.

Bendinello's expertise in trade and finance was apparently valued by the Genoese Republic: in 1498 he was a member of the ufficio della moneta, an anziano in 1499 and in 1500 a member of the ufficio mercanzie (the body which controlled mercantile activities and arbitrated in business disputes) and of the ufficio clavigeri (holders of the keys to the chest containing Genoa's most holy relic, the sacro catino, but also responsible for the comune's treasure chests).