The sources consulted agree that this surname derives from the medieval given name Nello, a hypocoristic formed by aphaeresis from longer names such as Antonello, Brunello, Giovannello, Leonello, or Lionello.

E. De Felice notes that the surname is frequent in Tuscany and sporadic in central Italy. E. Rossoni documents its establishment as a surname in Siena during the 14th century, attested by the notary Domenico Nelli, and in Florence toward the end of the same century with the painter Pietro Nelli. Rossoni further specifies that the surname shows specific, localized areas of concentration in Tuscany — between the areas of Lucca and Pisa — and in Lazio — between Rome and the area of Frosinone.