According to E. De Felice, the surname Agnelli is widespread from Tuscany towards northern Italy, with regional variants such as Aniello in the Neapolitan area and Agnello or Aniello in Sicily; forms such as Agnelutto and Dagnelùt are peculiar to eastern Veneto and Friuli-Venezia Giulia. It has as its base the personal name Agnèllo (Neapolitan aniéllo), derived from the noun "agnello" ("lamb"), used especially as a symbol of Christ and his sacrifice for humanity, as well as of purity and Christian faithfulness. This symbolic value explains its spread as a name in the Christian tradition.

For his part, E. Rossoni notes that Agnello was a fairly widespread given name in the Middle Ages, especially in central and northern Italy, which over time gave rise to the surname from the descendants of the original bearer. He also adds a possible alternative interpretation of the nickname type, linked to the adjective "agnello" in a figurative sense, to indicate a person of a meek, timid or gentle character.

Finally, F. De Laurentiis agrees that the surname derives from the name Agnèllo, widely spread from Tuscany northwards, and again highlights its strong symbolic charge within the Christian tradition, associated with the figure of Christ and with values such as purity and faithfulness.