The authors agree that this surname derives from the given name Cristoforo, whose classical form is the Greek Christophóros, Latinized as Christoforus. The central meaning is "bearer of Christ", although with nuances according to each source.

E. De Felice specifies that the name is documented as a surname between the 10th and 11th centuries, in forms such as Cristoforus, Cristofalus and Cristofanus, and that the Greek Christophóros alludes specifically, with reference to the Eucharist and to the consecrated host, to "the one who carries Christ within himself". He also notes a differentiated geographical distribution: the type Cristoforo is peculiar to central Italy, with Tuscan and mainly Emilian presence; Cristofaro and Cristofalo correspond to southern Italy, as do the patronymics with De or Di; and Cristofolo and Cristofano are predominantly Venetan forms.

S. Vannozzi adds that the name is also a hagionym and theonym sustained since the Christian Middle Ages, and that the diffusion of the surname and its variants intensified from the 10th and 11th centuries thanks to the cult of numerous martyrs named Saint Christopher across different periods until the 16th century. He also observes that the surname Fanelli, spread in the Riccia area, in Molise, is a diminutive originated in Cristofano, through the intermediate form Cristofanelli.

A. Bongioanni highlights the enormous popularity of the name and enumerates the most characteristic Venetan dialectal forms: Toffolo and Tofano, which gave rise to surnames such as Toffoli, Toffaloni, Toffanin, Follini, Fulin and Foratti. He also proposes that the Piedmontese surname Faletti could have this same origin. He warns, on the other hand, that the surnames Fanelli and similar ones can derive both from Cristofano and from Stefano, and that forms such as Toffolo sometimes converge with the name Teofilo.

V. Blunda records the surname in Sicily and describes it as a compound of the Greek Cristos with foros, "bearer", which became a surname from its use as the baptismal name of an ancestor.