The consulted works concur in deriving this surname and its many variants from medieval nicknames built on mosca ("fly"; in Sicilian musca, in Sardinian muska, plural muskas), with motivations rooted both in the literal meaning of the word and in its figurative senses, among them "small and ungainly, or annoying, person." This last figurative use is also noted independently: it is recorded that the word mosca, meaning "fly," served as a nickname to indicate an annoying person.

E. Rossoni adds that a direct derivation from the medieval personal name Mosca is equally possible, and that the transformation into a surname is documented as early as 1172 in the Annales Pisani.

E. De Felice notes that the surname presents altered forms such as moschella, moschina, moschino, and moscone. For the types Moscardo and Moscardino, De Felice proposes the bases moscardo and moscardino, regional names for certain species of sparrowhawks and falcons and for small octopuses, respectively. The forms beginning with Mu- are characteristic of Sicily and southern Calabria, while Muscas is specific to Sardinia, and apocopated forms correspond to the Veneto. Moscariello is specific to Campania.

Regarding geographic distribution, the base surname Mosca is spread throughout Italy. Rossoni specifies that Moschella is proper to the south — found in the areas of Naples, Avellino, and Salerno, in the areas of Vibo Valentia and Reggio Calabria, and in the areas of Messina and Catania — while Moschelli and Moschello appear to be Sicilian, and Moscuzza is typical of the area of Syracuse.