The scholars consulted agree that this surname derives from the place name Milazzo, a city in the province of Messina in Sicily. E. De Felice adds that it may also come from the demonym Milazzòtto, formed with the suffix of Greek and Modern Greek origin -òtes.

F. Miranda offers the most detailed etymology of the place name itself. Milazzo is the ancient city Hellenized by the Greeks of Zancle, known in Greek as Mylai and in Latin as Mylae, words which according to Pellegrini mean "mill." In the Byzantine period the form became Mylàs and in Arabic Milàs, whose ending in -s gradually evolved into -zzo. A second interpretation, proposed by Pensabene, links it to Mylarum statio, "embarkation station of the mill," while a third, following Cappello-Tagliavini, derives it from the Greek mylákion, "millstone."

E. Rossoni records an additional hypothesis: that the surname may have arisen as a nickname for a miller, connecting it to the Greek word mylax, "millstone" — a derivation that finds indirect support in the same etymological cluster Miranda attributes to the place name. Miranda further notes that, beyond Sicily, the surname is present across Lombardy, Piedmont, Lazio, Tuscany, Emilia-Romagna, Liguria, and Veneto. It is also considered typical of the commune of Messina.