The authors agree that the surname Leone derives from the Latin leo, leonis, which means "lion". In medieval Italy it was used both as a personal name and as a byname, associated with qualities such as strength or courage, and in time it became fixed as a hereditary surname. Its spread was favoured by the prestige of saints and popes who bore that name.

F. Miranda specifies that the surname derives from the Latin cognomen Leo-Leonis, which in Christian circles took hold especially through the cult of Saint Leo the Great, pope in the 5th century. He further notes that Leo and Leone also functioned as surnames of Jewish communities, as a translation of the Hebrew name Yehūdā (Judah), to which tradition —though without linguistic foundation— attributed the meaning "lion". A. Bongioanni likewise stresses the use of the name among Jews, and mentions as derivatives Leonzio and the diminutives Leonello and Lionello.

E. Rossoni adds that the origin of these surnames may further be linked to the heraldic sphere, that is, to belonging to the household of someone whose coat of arms included lions. Rossoni places Leone as an absolutely pan-Italian surname, while Surnames in Italy notes its particular frequency in the South (Campania, Calabria, Sicily), with a presence also in the centre and the north. Miranda agrees with that distribution and adds specific areas in Puglia and in various provinces of Sicily.

Among the surnames related by the same root are Leoni, Leonetti, Leoncini, Lionetti, Leonello, Leonini and Lioni. Rossoni places Leoni in central-northern Italy and in Sardinia, and Leoncini with a core between the Genoa and Alessandria areas, as well as another in Florence. Bongioanni and Surnames in Italy agree that these forms share the meaning linked to the "lion", although many arose independently in different places and periods, so that they do not necessarily imply kinship among them.