This region includes all of Italy south of the Alps. It is, of course, dominated by Rome. However, most of the actual pilgrims, as opposed to those going to Rome on Church business, actually visited Rome en route to the Holy Land. Those taking ship from the Apulian ports could visit Monte Sant'Angelo in the Gargano on the way from Rome. Similarly, those crossing the east side of the Appennines en route to Rome could make the short detour via Assisi or a somewhat longer detour via Loreto.
In the north of the region is the Po valley. Two routes cross this from west to east: through the northern side of the valley from the main Alpine crossing at Susa via the main city, Milano, to Verona, Padova and Venice; and along the northern edge of the Appennines, from Milano (or Vercelli) via Bologna to Rimini, the road known to the Romans as the Via Emilia. Connecting these two are various routes linking the Alpine crossings with Bologna or the Ravenna/Rimini area.
To the south of the Po lie the Appennines. There were three major routes across this:
- The main Roman crossing was the Via Flaminia, from Rimini and Fano, and through the Intercisa tunnel (still in use nearly 2,000 years later). This was the route used by the Bordeaux pilgrim on his return journey (he did not go via Rome on the way out). Because it was easy to make a detour via Assisi, the Flaminia was also used by Franciscans such as Rigaud, who used it on his outward journey. It was also used by pilgrims coming from or through Venice and Ravenna, as indicated in the Romweg-Karte and Estienne.
- In the west, the Lombards, journeying from Pavia to their possessions in S Italy, used the pass later named after them, Mons Langobardorum or Monte Bardone (1041m). This was used by Sigeric, and continued to be used in later centuries, such as by Nikulas, Emo, and Barthélemy Bonis. Matthew Paris also has Monte Bardone as an alternative.
- For those coming from the Adige/Etsch valley, a route between Bologna and Florence is the obvious way. In the later Middle Ages, as Florence gained pre-eminence among Tuscan cities, this also seems to have been favoured by those coming from the western passes; Emo's return, Annales Stadenses on the St Gotthard route, de la Broquière, and Estienne all use this.
- A more direct route from Ravenna over the Passo di Serra (1150m), which Matthew Paris gives as an alternative, and also used by Wey on his return. Interestingly, the Serra was also used by the Annales Stadenses for not only the Brenner route but also that from Mt Cenis; this is claimed as a better route than one south from Bologna.
- A route crossing from Susa to the coast at Savona, as used by both Rigaud on his return journey and Purchas on the outward journey.
To the south of the Appennines, the routes all converge on the route which runs along the Ligurian coast via Genova, and on to Lucca or Pisa, then inland to Siena and Rome. This forms a sort of backbone of routes south of the Appennines, and is the basis for the modern revival of pilgrim routes to Rome called the Via Francigena. The Bruges Itineraries specifically recommend going by ship from Savona/Genova to Pisa, as the coastal terrain in the Cinque Terre makes travel difficult.