The authors agree that the surname derives from the name of Greek-Byzantine tradition Epiphánios, in turn linked to the Greek verb epipháinesthai, which means "to appear" or "to manifest oneself". E. De Felice specifies that this name, continued also through the Latin adaptation Epiphanius, originally designated a person whose merits and actions induced a divinity to become visible or to manifest itself with evident signs.

E. Rossoni provides examples of the ancient use of the name: Epiphanios was bishop of Grado in the 7th century. The first records of its transformation into a surname are documented in Benevento already in the 13th century, with one Roffredo Epifanio as a jurist in the imperial court of Frederick II.

As for the geographical distribution, Rossoni distinguishes three variants. Epifani is typical of the Salento area —the southernmost zone of the region of Puglia, in the south of Italy—. Epifanio, considerably rarer, appears in a scattered way throughout the south. Epifano presents specific zones in the province of Pescara, in Sulmona —L'Aquila area— and in the Catanzaro area, specifically in San Mango d'Aquino.