The earliest reference to the monastery is made in a document of 1333, a period during which it was a fief of the Latin Patriarchate of Constantinople. It has also been argued (Stergios Spanakis) that the establishment of the monastery is linked with the miraculous icon of Our Lady, which is now kept in the church of San Alfonso in Esquilino, Rome. The icon of our Lady Kardiotissa has been associated with miraculous properties, reference to which was already made in 1415 by Chr. Buondelmondi. According to tradition, it has been moved or stolen many times, but each time it returned on its own. In the period of Venetian domination, the icon was stolen by a merchant and moved to Rome. In 1735 it was replaced by another icon, of a different iconographic type, which is nowadays regarded as equally miraculous. In 1720 the monastery was turned into a stavropegic one, following an initiative of the Magganaris family, who restored it. In 1866 and 1867 it was a Cretan rebel base.