The authors agree that this surname derives from the place name Giussano, a locality in the province of Milan, in Lombardy. E. De Felice characterizes it as a Lombard surname formed directly from that place name. E. Rossoni specifies that its fixing as a surname is documented in Milan in the 17th century, with the notary Giovanni Pietro Giussani, and notes that the surname is typical of the area north of Milan and of the Como area.

As for the more remote origin of the place name, Giussano would be a Roman predial toponym derived from a personal name, possibly Cluttius, Clustius or Justus. The medieval form of the name appears as Gluxiano or Gloxiano. The family that took its name from this locality is held to appear already in documents of the 9th century, and by the end of the 12th century its members occupied a prominent position in Milanese society, ranked among the valvassores, that is, the lesser aristocracy of Milan whose status derived from bonds of vassal dependence.