The authors agree that the surname derives from the dialect term santolo, which in several Italian dialects designates the godfather of baptism or of confirmation. E. Rossoni specifies that the word goes back to the late medieval Latin sanctulus, with the same meaning.

E. De Felice notes that santolo is an appellative in current use mainly in the Venetan, Friulian and Triestine area, although in past times it was more widespread. Rossoni, for his part, documents the geographic distribution of the different forms of the surname: Santoli presents a line in the Bologna area and its main nucleus in the Avellino area, with presences in Rome and in the Foggia area; Santolin is concentrated between the Vicenza and Treviso areas; Santolini presents independent origins in the Venice area, in Emilia-Romagna and in the Marche.

De Felice also mentions that the forms with the suffix in -in are characteristic of the north-east of Italy, in the regions of Veneto, Friuli-Venezia Giulia and Trentino-Alto Adige, while other variants are documented in Emilia-Romagna and Tuscany.