The authors agree that the surname derives from the place name Caltagirone, a city in the province of Catania (Sicily), whose name comes from the Arabic Qal'at-al-ghiràn. E. Rossoni interprets that etymon as "castle of the grottoes", while F. Miranda proposes the translation "castle or rock of the vessels".

Miranda also notes that, in some family groups that bear the name of a city, there may also be a Hebrew origin, as frequently occurs with surnames of this type.

Both authors agree that the surname is typical of centre-western Sicily, with a secondary nucleus in Rome. Miranda specifies that, within Sicily, the greatest concentration is recorded in the Agrigento, Palermo, Trapani, Caltanissetta and Enna areas, and that the surname also extends through other regions such as Lombardy, Lazio, Piedmont, Tuscany, Emilia-Romagna, Liguria, Campania, Apulia and Sardinia.