The authors agree that the surname derives from the place name Messina, a city of north-eastern Sicily, and that it indicates the place of provenance of the first bearers. F. Miranda specifies the historical origin of the name: the ancient Greek city called Messenion or Messene, so named in honour of Messenia, the homeland of Anaxilas, tyrant of Reggio, who conquered it in 491 BC. G. P. Holmes adds that the Greek term messene, Latinized as Messana, meant "curve, sickle" and, by extension, "strip of land in the shape of a sickle", in reference to the geography of the strait.

E. De Felice notes that from the same place name derive the variants Messinése, Messinèo and Missinèo, the last two proper to the Greek-speaking Calabrian areas, where the suffix -èo comes from the Greek -àios. He further indicates that the form Messinèo may also derive from the place name of the same form in the province of Palermo.

E. Rossoni and Miranda agree in noting that part of the diffusion of the surname is linked with families of Jewish origin. After the decree of 1492 which obliged the Jews to leave the territories of the Spanish Crown —which included Sicily— or to convert to Catholicism, many Hebrew families adopted the names of commercial cities such as Messina or Genoa in order to remain on the island without being identified.

The surname is present throughout Italy, with a great concentration in Sicily and significant cores in Lombardy, Campania, Piedmont, Lazio and Calabria.