The authors differ on the origin of the surname. In Surnames in Italy we gathered several hypotheses: a derivation from the Latin bos ("ox"), supported also by the 1839 Milanese vocabulary of Cherubini, which records the dialectal word boz meaning "small ox" and also "person of little judgement"; and an alternative etymology proposed by Merati, who traces it back to the Germanic Bozo, with the sense of "bad". In the Middle Ages, forms such as Busus, Bossus, Bossius and de Boso are documented as personal names and surnames.

R. Brondolo, on the other hand, proposes a different explanation: the surname would derive from Jacobossi, an apocopated form of Jacopo or Giacomo, following the tendency of certain Italian surnames to lose their initial syllable and keep the final one. The variant Bosso, with the ending in -o characteristic of the Piedmont area, would respond to the same origin.

From the historical and geographical point of view, Surnames in Italy documents the presence of the surname in the Milan area from the 12th century: in 1170 a Tosabos Bossius figures as consul of Justice, and in 1398 Bossi families are recorded in several parishes of the Milanese diocese, among them Gallarate, Varese and Seveso. Brondolo notes that the surname is very widespread in the Lombardy area.