The authors agree in noting that the surname Pennisi has an origin linked to the place name Pennisi, the name of a district of the municipality of Acireale, in the province of Catania, Sicily. E. De Felice puts it succinctly, indicating that the surname was formed from that place name located in eastern Sicily. F. Miranda expands this information by specifying that this district sits on a territory that was formerly occupied by the forest of Aci.

Miranda further adds a second line of interpretation: Pennisi would function as an ethnic surname derived from the place name Penna, with the sense of "coming from Penna," a place name shared by several Italian localities, among them Penna in Teverina in the province of Terni, Monte Penna in the border area between Liguria and Emilia-Romagna, Monte Penna between Umbria and the Marche, Penna San Giovanni in the province of Macerata, and Penna Sant’Andrea in the province of Teramo.

Surnames in Italy further mentions two unconfirmed etymologies: one connecting the surname with the Latin penitus, with the sense of "deeply" or "inwardly," and another linking it to the Greek penein, with the meaning of "to work hard" or "to strive." The ending in -i would respond to a habitual practice in the Middle Ages, by which surnames were pluralised to designate a family as a whole.

The surname is concentrated mainly in Sicily, with a particularly notable presence in the province of Catania. Miranda notes that it also appears, with less density, in regions such as Lombardy, Lazio, Liguria, Piedmont, Calabria, Tuscany, Emilia-Romagna, Apulia and Veneto. The variant Pennise, according to Surnames in Italy, is very infrequent and probably the result of transcription errors.