The authors agree that this surname derives from the place name Lampugnano, a locality now absorbed into the metropolis of Milan, in the region of Lombardy. The place name is held to be of Roman predial origin and to contain the personal name Lamponius, so that the original rus lamponianum evolved in time into Lampugnano, which subsequently became a surname.

E. Rossoni notes that the first documentary traces of the family go back to the year 1000, and cites a notarial deed of 1108 in which a certain Guitardus, son of the late Anselmi, identifies himself as qui vocor da Lampugnano, of the city of Milan, when making a donation to the church of San Giorgio. Rossoni also highlights Umbertino da Lampugnano, lecturer in canon law at the University of Pavia between 1372 and 1381, and subsequently Master General of revenues and ducal counsellor from 1395.

The Lampugnani family is further held to have been enrolled in the Matricola Nobilium Familiarum of 1377, whose members had the right of passive election as canons of the Duomo of Milan. Among notable historical episodes, it is recalled that Andrea Lampugnani was one of the three young men who assassinated Duke Galeazzo Maria Sforza in 1476.