The surname Zaccagnini (and related forms) derives, according to E. De Felice and E. Rossoni, from nicknames formed from dialectal words of northern Italy. In particular, it is linked with the old term zaccagnare (Emilian zacagnèr, Lombard zacagnàr), which referred to one who "gets by as he can", does improvised or low-quality work. From this same root comes zaccagnino, which in the popular sphere also designated a character of the theatre —similar to the second zanni of the Po Valley tradition and of the commedia dell'arte— characterised as a clumsy, naive or buffoonish servant.

In this sense, the surname would have arisen as a byname applied both to persons of a rustic or unrefined character and, in other cases, to individuals of a quarrelsome or pugnacious temperament. The diffusion of the term is documented already in 15th-century Lombardy, where, for example, a Giovanni Pietro da Carcano, known as "Zaccagnino", is recorded.