E. De Felice and F. De Laurentiis agree that the surname was formed from the name Ruffo, derived from the Roman cognomen Rufus, formed in turn from the adjective of Sabine or Italic origin rufus, equivalent to the Latin ruber ("red [of hair, of beard]").

De Felice specifies that the name, with the diminutive Ruffolo, continues at least in part —through the Latin of the High Middle Ages Ruffus and Ruffolus— the Roman cognomen Rufus, with the diminutive Rufulus. He also considers it probable that, in the south, the surname has a Germanic etymology and origin, especially for the great Calabrian family of the Ruffo, which would have arrived in southern Italy with the Normans.

De Laurentiis notes that the surname is diffused in the south.