The authors agree that this surname derives from a nickname, quattrocchi ("four eyes"), applied to someone who wore glasses. E. De Felice notes that the nickname was common in various regions, as illustrated by the Neapolitan form quattrócchie, and that the surname is concentrated mainly in Calabria and eastern Sicily. F. De Laurentiis and G. P. Holmes agree with this interpretation without adding new elements.

E. Rossoni shares the origin in the use of glasses and notes that the surname seems typically Sicilian, although it also records a significant presence in the Rome area. For his part, F. Miranda broadens the geographic distribution: besides Sicily —where it is present in practically all its provinces, with a special concentration in Catania, Messina, Palermo, Caltanissetta and Enna— the surname appears in Lazio, Lombardy, Piedmont, Calabria, Campania, Emilia-Romagna, Tuscany and Liguria.

Miranda also gathers additional semantic interpretations: according to the linguist Caracausi, quattrocchi would have functioned as an auspicious name with the sense of "may he be very shrewd or perceptive"; and according to De Criscito, the term alluded in a figurative sense to one who revealed private confidences, given that the expression a quattrocchi means "face to face," that is, without witnesses.