F. Miranda proposes two hypotheses on the origin of this surname. The first derives it from a Greek-Calabrian nickname μέλισσαρες (melissares), with the meaning "honey-dealer", in reference to the trade of beekeeper or honey-producer that its first bearers are said to have practised. The second hypothesis links it to the place name Minissale, a district of Messina situated between Gazzi and Contesse: those lands are said to have constituted a dominicato —that is, a property free of feudal ties which generated seigneurial rents—, whose name evolved from the Latin dominus ("master, owner") to dominissale and finally to minissale, later becoming a surname.

G. P. Holmes relates the surname to ancient Greek, with the meaning "honeycomb". For his part, F. De Laurentiis considers it derived from the given name Menico.

It is a surname typical of Sicily, present especially in the Catania area —in localities such as Misterbianco, Bronte and Biancavilla—, in the Messina area, in the Syracuse area, in the Enna area and in Palermo. Outside Sicily, Miranda notes its scattered presence in regions such as Lombardy, Piedmont, Lazio, Tuscany, Emilia-Romagna, Veneto, Campania and Sardinia.