Built in 1539 after the Orthodox community had obtained independence from the Patriarch, on a plan by the architect Sante Lomardo, the church features a single nave interior with a hemispheric central cupola.
To the back is an iconostasis - customary in the Greek Orthodox rite - richly decorated in marble and paintings of the Greek-Byzantine school.
Next to the church, in a building by B. Longhena - the Hall of the Confraternity of St Nicholas of the Greeks - is a collection of Greek icons and works by Greek and Venetian painters.
These two edifices indicate the high standing of the Greek community that had already been established here in the 11th century (only the Jewish community was more numerous).