The authors differ on the etymology of the surname. E. De Stefani links it to the Friulian mazzûl, a term designating the "wooden mallet for striking barrels", which was also used as a nickname until it became a surname. Alternatively, De Stefani proposes relating it to compounds formed by mazza- ("kill-") plus a second element, a use of nicknames documented until the 16th century in the Socchieve valley —such as maza fadiga, "kill-effort", that is, an idler—, which would bring it close to the Venetan mozafadiga. He rules out, by contrast, a connection with the Latin madium ("May"), which in Friulian gave mài.

E. Rossoni, for his part, proposes that the surname would derive from diminutives of the Germanic name Mazzi or Mazzo, although he also considers possible an origin in the nickname mazza, both in the sense of "club" and in that of "to kill". Rossoni documents the name Mazzolinus in the year 1000 at Tivoli, and recalls the painter of the Ferrara area Ludovico Mazzolino (1480–1530).

As for its geographical distribution, De Stefani notes that the surname is found in central and northern Italy, with a high frequency in Carnia —the mountainous area of northern Friuli, in the province of Udine— and a presence documented from the middle of the 14th century at Venzone. Rossoni agrees on the presence in the Udine area and adds cores in the Brescia, Milan, Bologna and Forlì areas, and in the region of the Marche. The variant Mazzolino, according to Rossoni, appears to be proper to north-western Italy.