Built by the Italian–Jewish community of Apulia during the Middle Ages,[3] the building was acquired by the Roman Catholic Church in 1380 during a wave of antisemitism and served as St. Maria's Church (Italian: Santa Maria in Scolanova) until it was deconsecrated and returned to the Jewish community in 2006.

[8] In 2006 the Scolanova Synagogue, which had been standing as an empty and disused church since the 1950s, was de-consecrated and returned to the Jewish community.

The individuals principally responsible for the reconsecration of the synagogue were Professor and Francesco Lotoro, descendants of Italian Anusim.

The community now includes descendants of Neofiti (Italian crypto-Jews) and San Nicandro Jews.

[7] The building next door once contained the synagogue's women's gallery and, in the basement, the stairs and pool of the medieval mikveh survive.