In the course of the 16th century, a Jewish community settled in Pitigliano, increasing notably when Pope Pius IV banned Jews from Rome in 1569. Under Medici rule, its members were moved into a tiny ghetto, where they remained until 1772. From then until well into the following century, the local community of 400 flourished, forming the largest Jewish community in Italy and leading to the town being dubbed 'Little Jerusalem'. By the time the Fascists introduced the race laws in 1938, most Jews had moved away; only 80 or so were left and precious few survived the war. Those that did survive were hidden from the Fascists by locals.

To visit the old Jewish ghetto, head down Via Zuccarelli and turn left at a sign indicating La Piccola Gerusalemme, a small museum of Jewish culture incorporating a tiny, richly adorned synagogue (established in 1598 and one of only five in Tuscany), ritual bath, kosher butcher, bakery, wine cellar and dyeing workshops.