The authors agree that the surname derives from a dialect term of northern Italy linked to the idea of "mace" or "large head". R. Brondolo specifies that the dialect word mazzucco was applied figuratively to a "person with a large head, squat". Along the same lines, it is recorded that mazzucco in Venetian dialect and mazucch in Milanese dialect mean "head", which confirms the nickname origin of the surname.

E. Rossoni places the surname in the strip comprising the Como, Milan, Bergamo and Brescia areas, and derives it from the medieval name Mazuchellus, which in turn could descend from Mazuchis, a medieval family designation. He notes that the personal name Mazuchellus is documented at Modena from 1182, and that in the municipal library of Bergamo a notarial deed of 1272 attesting it is preserved. He further mentions the Renaissance painter known as Mazuchellus Morazonus.

Earlier testimonies are also recorded: in the Historiae Patriae Monumenta the form Ursulo qui Mazuco vocatur appears in the year 882, and in the list Mille Hominis Pergami of 1156 a Malcoatus filius Mazuchelli figures, which makes this one of the most anciently documented surnames in Italy.