The authors agree that this surname has two main hypotheses of origin. The first links it with the Greek term despotes, meaning "master of the house" or "lord", of which Spoto would be an aphaeretic form, that is, arisen through the fall of the initial syllable. The second hypothesis proposes a toponymic origin, derived from the name of a locality.

E. Rossoni notes that the surname has a clear noble lineage and that the Sicilian writer Luigi Pirandello used it in his novel I vecchi e i giovani as the surname of a family with noble pretensions. He also points out that the reference place name would be found in the province of Agrigento.

F. Miranda, following Vezzelli, specifies that this place name corresponds to the Masseria Spoto, a frazione of the municipality of Sant'Angelo Muxaro, in the province of Agrigento. Miranda notes that this is a typically Sicilian surname, very widespread in the Agrigento area —in localities such as Agrigento, Porto Empedocle, Canicattì and Alessandria della Rocca, among others—, in the Catania area —with a presence in Catania, Acireale, Paternò, Aci Catena and Aci Castello, among others—, in the Messina area —Milazzo, Messina and Pace del Mela—, in the Palermo area —Palermo, Termini Imerese and Bagheria, among others—, and with a known presence also in the Syracuse and Caltanissetta areas. Miranda adds that some families with this surname are also attested in Lombardy, Piedmont, Tuscany, Lazio, Emilia-Romagna, Liguria, Campania, Apulia, Calabria and Veneto.