E. Rossoni notes that Luparini is a very rare surname, proper to the Perugia area, while the variant Luperini, equally scarce, is located in the Pisa area. Both forms derive from the medieval name Luparinus. Rossoni documents its historical presence in two testimonies: a certain Luparino figures among the hostages taken by Frederick Barbarossa in 1155 after the razing of Spoleto, and a Fulvio Luparino appears among those tried by the Holy Inquisition in June 1590.

V. Blunda proposes a different etymology of Sicilian dialect root: the surname would derive from the word luparìnu, with the meaning "distrustful, suspicious, wolfish in manner", an adjective that transfers the elusive character of the wolf to human conduct. According to Blunda, the surname would have arisen as a nickname applied to a person of surly manner or known for his wariness of strangers.

The two proposals are not necessarily mutually exclusive: Rossoni's points to an origin in the medieval given name Luparinus, with a documented presence in Umbria and Tuscany, while Blunda's suggests an independent appellative origin in Sicily, which indicates that the surname shows multiple independent clusters of origin (ceppi) in different regions of Italy.