P. Durante notes that the surname has a Greek origin, derived from mousikós, with the meaning "musician".

V. Blunda offers a more detailed perspective of regional scope: he considers it a surname of Sicilian origin, coming from the dialect word mùsico, with the sense of "singer, chapel eunuch". The term referred to the castrated soloist of the Baroque musical chapels. As a surname, it could have arisen from the nickname applied to the ecclesiastical servant devoted to singing, or else to the descendants of one who was recognized for that family trait.