It runs northwards from Genoa on the Ligurian coast, over the Apennines, and across the wide plain of the Po valley to the environs of Lake Maggiore and the mouth of the Val d’Ossola.

It proceeds north-east and follows the shore of Lago Maggiore with exits for Arona, Brovello-Carpugnino, Baveno - Stresa, Verbania and Gravellona Toce.

From here the strada statale 33 del Sempione [it] continues the route northwards, initially as a superstrada (a form of expressway), to Domodossola and then via the Val Divedro to the Swiss border, affording access to the Simplon Pass.

It forms part of the 1,547 km European route E25 which connects Hook of Holland in the Netherlands to Palermo in Sicily.

The road was built to provide a route for traffic from Domodossola and the Simplon Pass to Milan and thence to the parts of the peninsula to the east of the Apennines.