The authors agree that Di Stefano is a patronymic surname that designates the son or daughter of a father named Stefano. F. Miranda specifies that the name Stefano derives from the Greek Stéphanos (Στέφανος) and from the Latin Stephanus, which literally means "crown" and by extension "crowned". Before the arrival of Christianity, the crown was a symbol of victory; with Christianity, the name became associated with the cult of Saint Stephen and with the crown of martyrdom.

G. P. Holmes notes that the surname spread from the Christian Middle Ages thanks to the cult of Saint Stephen, which explains its wide geographical distribution. Miranda adds that Di Stefano is widely spread throughout Sicily, with especially prominent presence in the Catania, Ragusa, Messina, Palermo, Syracuse, Trapani and Enna areas. Outside the island, the surname is also recorded in Lazio, Umbria, Abruzzo, Molise, Lombardy and Piedmont.