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.