The traditional foundation date for this church is that of the city itself: 25 March 421. It has undergone several radical reconstructions since then, the last in 1601. Nonetheless, the original Greek-cross plan was always preserved, as were its minuscule dimensions. The interior has columns of ancient marble with 11th-century Corinthian capitals.
In 1177, Pope Alexander III granted plenary indulgence to all those who visited the church on Maundy Thursday; among the eager visitors every year was the doge. The special role of this church in Venetian history was given official recognition after 1532, when Pope Clement VII bestowed the patronage of the church on the doge, effectively annexing it to the Ducal Chapel of St Mark's. The church frequently hosts evening concerts.
According to Francesco Sansovino (son of the architect and author of the first guide to the city, in 1581), the brick dome may have been a model for the domes of St Mark's.