E. Rossoni notes that the forms Cane and Cani would derive from the medieval name Cane, recalled in the historical figure of Cangrande della Scala (1291–1329), lord of Verona. Rossoni documents signs of its transformation into a surname in the Valle Anzasca, where in 1496 three brothers, the counts Cani coming from San Pietro, in the Aosta Valley, settled to work in gold mines. For the variant Canè, the same author gathers an alternative interpretation: it would derive from the local name Canè, equivalent to the Latin cannetum, meaning "reed bed".

A. Bongioanni agrees in noting the origin in the medieval name Cane and mentions its use in the della Scala family. He adds that, in the Middle Ages, the name should not have been considered offensive, and suggests that it could be linked with some surnames recorded under the entry Ascanio.

V. Blunda provides a different etymology for the surname in Sicily: he considers it of Arabic origin, derived from the etymon qani, meaning "red" or "of the red colour", used probably as a nickname referring to the ruddy complexion or the colour of the hair. The surname therefore presents independent clusters of origin according to the region: one of Latin or medieval root in northern and central Italy, and another of Arabic root in Sicily.