It originally comprised four elements, of which three survive, now all separated: a main panel of the Crucified Christ with the Virgin Mary, Saints and Angels which was bequeathed to the National Gallery, London, by Ludwig Mond, and a three-panel predella from which one panel is lost; the two surviving panels are Eusebius of Cremona raising Three Men from the Dead with Saint Jerome's Cloak in the Museu Nacional de Arte Antiga, in Lisbon, and Saint Jerome saving Silvanus and punishing the Heretic Sabinianus in the North Carolina Museum of Art.

The side chapel was dedicated to Saint Jerome, where most of the painting's original pietra serena stone frame survives including the inscribed date 1503.

The main panel portrays the Crucifixion of Jesus, against a background of hills in the Umbrian countryside, with a view of Città di Castello in the distance.

To the proper left (Jesus' right) his mother Mary stands behind the kneeling Saint Jerome, who is holding a stone with which the hermit would piously beat his own chest.

In the Mond Crucifixion, Raphael has used Perugino's technique of cross-hatched shadows, but also used his fingers to smear and soften the wet paint in places, leaving some detectable fingerprints.

Saint Jerome is holding back the arm of the executioner ready to behead bishop Silvanus, but the heretic Sabinianus has been miraculously decapitated instead.

At the Fesch sale in 1845, it was sold to the Principe di Canino, and quickly bought by Lord Ward (later Earl of Dudley).