In the second half of the 16th century a small group of Jews of Italian origin began to form from central and southern Italy and more particularly from Rome. In 1575 they built their own Synagogue, the Scola Italiana, in the Campo di Ghetto Novo in front of the present Rest Home. In 1633 the Ghetto Novissimo, in the parish of St. Ermacora and St. Fortunato (San Marcuola), was added to the Ghetto Novo and the Ghetto Vecchio located in the parish of San Girolamo.
It was a rather small area enclosed by the calle di Ghetto Novissimo and that of the Ormesini and formed by two calli which meet: on the jambs of the entrances can still be found traces of the doors which closed off also this third Ghetto which differed considerably from the other two in the importance of its public buildings.
Thus various small communities grew up in the Ghetto, each taking the name of a University or Nation and each quite separate and completely autonomous from the others. Each had different regulations and lived accordingly for each group had brought with it its own customs and habits and also its own religious traditions.