The authors agree that the surname derives from mancino, a term designating one who uses the left hand with greater skill than the right. E. Rossoni notes that it could be a nickname motivated by that physical characteristic of the ancestor, but he also considers possible a derivation from the Latin cognomen Mancinus —cited by Livy in Ab Urbe Condita when he mentions the consul Hostilius Mancinus— or else from one of the numerous place names Mancini or Mancino found in Italy.

Rossoni describes a broad geographical distribution for the various forms of the surname. Mancin is proper to northern Italy, with a marked presence between the Rovigo and Venice areas, northern Piedmont, western Lombardy and Emilia; its derivatives also appear between Rome and Latina. F. De Laurentiis specifies that, in Veneto, it represents a nickname of dialect origin.

The variants show differentiated distributions according to Rossoni: Mancina is concentrated in Calabria, especially at San Giovanni in Fiore and in the Cosenza area; Mancinelli extends across a central-southern strip covering Rimini, the Marche, Umbria, Lazio, Abruzzo, and the Campobasso, Benevento and Naples areas; Mancini is very widespread throughout the Italian peninsula, with the greatest concentration in the central strip, Campania and Puglia; Mancino predominates in Rome, in southern Italy and in Sicily, particularly in the Palermo area.