E. Rossoni proposes two lines of origin. In southern Italy, the surname would derive from a nickname based on the old term masto, a variant of mastro, with the sense of craftsman or master of a trade. In Veneto, by contrast, it could be linked to the activity of washerwoman practised by the founder of the line, relating it to the term mastella or mastello, which designated a vessel with handles for carrying laundry between two people on a pole, itself derived from the German Mast, "pole".

Rossoni notes that the surname shows areas of presence in the Verona, Vicenza and Padua areas, and another in the region of Campania. Of the related forms, Mastelli, absolutely rare, is proper to Veneto; Mastello, almost unique, appears in the Naples area and in the Benevento area.

F. De Laurentiis agrees in pointing to the Neapolitan term masto as the base, and specifies that this functioned at once as a nickname, an honorific title and an occupational name, derived from mastro, with the meaning "master" in the sense of a qualified officer or craftsman.