The authors agree that this surname derives from the Latin paganus, a term that in ancient Rome designated the inhabitant of the countryside or of the village (pagus). With the expansion of Christianity, the word acquired a second meaning: that of one who did not profess the Christian faith. This double sense —geographical and religious— explains that, during the Middle Ages, paganus was used both as a byname of religious value and as an appellative applied to peoples considered external to the Christian world.

F. Miranda notes that the surname and its variants (Pagana, Paganello, Paganelli, Paganetti, Paganetto, Pagani, Paganin, Paganini, Paganoni) do not exclude a toponymic derivation from one of the numerous place names with the root Pagan-, such as the locality of Pagani, in the province of Salerno. Miranda also indicates that the surname is fairly diffused in southern Italy, particularly in Campania, Sicily and Puglia, with specific areas in the Catania, Messina, Palermo, Enna and Caltanissetta areas, besides a presence in Lombardy, Lazio, Liguria, Piedmont, Tuscany, Calabria, Emilia-Romagna and Basilicata.

The surname is held to be of a pan-Italian character, with a historical concentration in northern and central Italy —Lombardy, Emilia-Romagna and Veneto—, and its use as a personal name is documented from the medieval period in notarial and ecclesiastical registers, with forms such as Paganellus or de Pagano, before becoming established as a hereditary surname.