The proposed study looks at the issue of contacts between Jews in Prague and Mantua, contacts which unfolded at many levels in the 16th century. Important Jewish communities which were large in population were formed in the 16th century in both cities, both reaching their greatest prosperity after the mid-16th century. This development was permitted in Prague, which became an Imperial Residence in 1582, by the policies of Rudolf II, who gave the Jews in Bohemia a more stable environment both legally and economically, thus contributing towards the multi-faceted development of the Jewish community. The peak of the Jewish community in Mantua occurred under the reign of Vincenzo I Gonzaga (1587–1612), whose court found a role for many figures of Jewish origin in the cultural and artistic sphere, and not just Jewish financiers. The study maps the network of personal, family and professional contacts which were in existence between members of the Jewish communities in Mantua and Prague. These connections were generally based on specific individuals who were respected in their communities and were part of the religious, political or economic elite within their Jewish communities. In the study, we endeavour to present some of these figures of religious and cultural life, and also representatives of the financial and business spheres who operated along the link between Renaissance Mantua and Prague. We also endeavour to explain and assess the political, cultural and economic reasons which directly or indirectly led to the establishment of these contacts and which influenced their establishment.