Self-sufficient Molise is Italy's newest region, determined independent in 1963. Its Iron Age Samnite population fiercely defended themselves from the Romans, staving off advances until about 290 BC. The archaeological museum in Campobasso, the region's capital, preserves rare artifacts from the warrior race, made nearly extinct once finally bested in battle. Southwest of the city lies Saepinum, a Samnite village occupied by the Roman conquerers.

Though once protected by Samnite walls measuring 3.7 m (12 ft) high and 3.0 m (10 ft) thick, Isernia has been destroyed and rebuilt 12 times, a victim of war, natural disasters and circumstance. Until 1979, concealed nearby were the ruins of a 700,000-year-old village, the oldest found in Europe. The Museo Nazionale della Pentria re-creates the site, where excavations continue. Deserted Roman ruins at Pietrabbondante offer an exclusive experience, and Venafro and Termoli are superb examples of medieval hill-towns. South of Termoli are Campomarino, Portocannone, Ururi and Montecilfone, Albanian villages where a rare dialect is spoken by modern descendants of their ancient and feared militia.