Designed round a novel architectonic skeleton, this canvas came to be the inevitable model and paragon for all the prestigious painters of the age, from Bellini, with his San Giobbe altarpiece, to Giorgione, the painter of the Castelfranco altar, and Alvise Vivarini, whose altarpiece was destroyed in the Kaiser Friedrich Museum at Berlin in 1945.

This particular work of Antonello's, which had so significant an influence on his artistic career, and also on the history of subsequent Venetian painting, disappeared from the Church of San Cassiano in the first decades of the 17th century. Ridolfi mentions it in 1648. Reduced to fragments, it reappeared in the collection of the Archduke Leopold William in Brussels, and was attributed to Giovanni Bellini. About this time, Teniers made copies and engravings of them. In 1700 three or so of the large fragments found their way to Vienna. The two side-wings remained unrecognised until 1928, when they were put on show by Wilde. The Madonna was displayed, attributed now to Bellini, now to Boccaccino (Wickhoff, 1893 and Berenson, 1916-17); the latter was the first to identify in this picture the centre-piece of the San Cassiano altar. Finally Wilde managed to trace the two lateral fragments and tried to reconstruct the whole (1929).

This ambitious altarpiece was probably Antonello's most influential work. It has come down to us as a fragment, although by means of old copies, the sensible reconstruction indicates that even before Giovanni Bellini, Antonello produced a characteristically Venetian altarpiece.