The authors agree that this surname derives from the medieval name Mannus or Manno, of Lombard origin, with the meaning "man". Both E. De Felice and E. Rossoni note that one of its possible paths of formation is the aphaeresis of medieval compound names such as Alemanno, Ermanno or Harimanno.

De Felice distinguishes the origin according to geographical area: in Tuscany, Manno would function as an apocopated hypocoristic of those compound names; in central and southern Italy, it would continue directly the Germanic name Manno; and in Sardinia it would represent an Italianized variant, not very frequent, of Mannu.

Rossoni adds that a derivation from a dialect modification of the Latin magnus is not ruled out, and supplies concrete documentary testimony: the Codice Diplomatico della Lombardia Medioevale records the form in the year 1088 at Sovere, and in the 15th century it appears at San Miniato, in the Pisa area, with the notary Alamanno Manni de Buiano. He further notes that the place name Manno, in the province of Reggio Emilia, shares the same onomastic base.

As for distribution, De Felice stresses the high frequency of the surname in Tuscany, where derived forms such as Mannelli, Mannini, Mannucci, Mannoni and Manneschi are also recorded. Rossoni specifies that the surname extends across the whole of central and northern Italy, with a notable presence besides in the Salento area —the southernmost zone of the region of Puglia, in southern Italy—, and that Manno appears in areas of Naples, Calabria and Sicily.