E. De Felice notes that this surname originated as a nickname from the adjective grande ("big, tall"), in reference to the physical build or height of the person, in contrast to surnames such as Piccoli. F. De Laurentiis agrees with this etymology and adds that the surname is widespread throughout Italy, with a high frequency in Emilia-Romagna. P. Canè reinforces the sense of the base term by noting that grande alluded to someone who was tall or of striking presence.

De Felice further supplies information on the formal variants of the surname by region: Grando, Grandis, De Grandis, Grandìn, Grandotto and Grandesso are proper to Veneto, while Lo Grande is recorded in Sicily.