The upper tier displays a Crucifixion flanked by the four evangelists. The middle tier shows the Virgin adoring the Child, flanked by four female saints: Lucy, Helena, Mary Magalene and Catherine of Alexandria.
The predella presents five episodes from the Invention of the Cross:

• Saint Helena arrives in Jerusalem
• Helena summons the Jews, who take counsel
• Judas, after initially refusing, is lowered into a well, then reveals the whereabouts of the True Cross and starts digging
• The True Cross proves itself by healing a boy
• Adoration of the True Cross; devils flee

The painting stood on the altar of the patron saint in the church of Saint Elena in Venice. The frame is original.

In the background of the panel there is a landscape of the region near the artist's birthplace, Conegliano. Cima used the identical view in the Virgin and Child in London.

For the Friday Office, devoted to the Cross, Jean Colombe represented the Revelation of the True Cross, as told in The Golden Legend. Because there was doubt as to which of the three crosses had served for the crucifixion of Christ, the Bishop of Jerusalem ordered each one to be placed in turn beside a dying woman. When she touched the True Cross, she was miraculously cured.

Among the group on the right is a figure wearing a pointed cap, who probably represents the Jew who knew the secret of the crosses' location.

The Exaltation of the Cross celebrates the recapture of the Cross by Heraclius.

On either side of the altar upon which the patriarchal cross is exhihited stand two men with flowing beards who hold long rods. Encrusted with coloured jewels, the cross rests on a green lizard whose tail entwines it; it is perhaps the "croix au serpent" ("snake cross") that belonged to the Duc de Berry.

Three monks wearing cloaks have come to adore it. Heraclius recalls St Louis, an ancestor of the Duc de Berry, who also carried, barefoot, relics of the True Cross.

The two saints, Helena on the left, stand against a diapered background, surrounded by a scrollwork border. Below them is a cluster of blacksmith’s tools and products of the forge, including many keys and padlocks along with horse-trappings complete with horse (at the right) and much else.

All of these, shown here against a squared pattern suggesting a chequered floor, are attributes of St. Eloi, who was a blacksmith and goldsmith in his earlier life, before he became eventually bishop of Noyon in France.

St. Helena holds her own attribute, a Tau cross representing the True Cross.