The first church here was built as a small oratory with a xenodochium, or guest house, at the end of the 6th century by the Byzantine general Belisarius.
The present church was rebuilt from the foundations 1570 - 1575, in the pontificate of Gregory XIII, after the pope gave the church to the Crociferi Brothers. The architect was
Jacopo del Duca, and the patron was Cardinal Cornaro. The inscriptions on the façade records the rebuilding. The present fabric of the church is from that rebuilding.
From 1670 the church underwent a complete renovation and decoration, including the ceiling vault frescoed, and in 1675 it was formally dedicated to the Immaculate Conception.
Pope Pius IX (1846-1878) granted the church and convent to the
Missionaries of the Most Precious Blood, who still serve the church.