The authors agree that this surname derives from the name Lupo, which in part continues the late imperial Latin cognomen Lupus (from the Latin lupus: "wolf") and in part was reformed in the early Middle Ages from the Romance term lupo. Its consolidation was favoured by the prestige of the corresponding Germanic names in Wolf- (from the Germanic *wulfa-, German Wolf: "wolf") and of the Lombard Lupo Lupone.

E. De Felice notes that both the name and the surname are documented from the early Middle Ages, especially in northern Italy, where dialect variants such as luv, luvu, lól, lóvo, lòuv, luvòt and lovàt appear, among others.

E. Rossoni broadens the picture and indicates that the surname Lupi is very widespread throughout central and northern Italy, while Lupo is pan-Italian. He also notes that Lupini shows two specific areas: one in the Bergamo area and another in that of Perugia; and that Luppi has its main core in the area of Mantua, Modena and Bologna, with another specific area in Milan and Como. The form Lupu, almost unique, would appear to be proper to the area of Molise and Puglia.

Rossoni further distinguishes several possible origins: besides the Latin cognomen Lupus —the most substantial source—, he notes the derivation from place names containing the term lupo or lupi, such as San Lupo in the Benevento area, Morlupo in the Rome area, and Montelupo, found both in the Florence area and in that of Cuneo. He also considers possible a derivation from nicknames linked to encounters or circumstances involving wolves.