St Jerome in the Wilderness (c. 1480) is an unfinished painting by Leonardo da Vinci, now in the Vatican Museums, Rome.

The painting depicts Saint Jerome during his retreat to the Syrian desert, where he lived the life of a hermit. St Jerome kneels in a rocky landscape, gazing toward a crucifix which can be discerned faintly sketched in at the extreme right of the painting. In Jerome's right hand he holds a rock with which he is traditionally shown beating his chest in penance. At his feet is the lion which became a loyal companion after he extracted a thorn from its paw. The lion, the stone and a cardinal's hat are the traditional attributes of the saint.

On the left-hand side of the panel the background is a distant landscape of a lake surrounded by precipitous mountains shrouded in mist. To the right-hand side, the only discernible feature is a faintly-sketched church, seen through the opening in the rocks. The church's presence may allude to Jerome's position in Western Christianity as one of the Doctors of the Church.

The composition of the painting is innovative for the oblique trapezoid form of the figure of the saint. The angular forms contrast with the sinuous form of the lion which transcribes an "S" across the bottom of the painting. The form of St Jerome prefigures that of the Virgin Mary in the Virgin of the Rocks. The rendering of the muscles in the neck and shoulders is seen as the first of Leonardo's anatomical drawings.

The panel has been reduced in size and the remaining part was cut in two at some point in its history and was reassembled for the early 19th-century collector, Cardinal Fesch, the uncle of Napoleon Bonaparte. Popular legend has it that the Cardinal discovered the part of the panel with the saint’s torso being offered as a table-top in a shop in Rome. Many years later, he found another piece being used as a wedge for shoemaker’s bench. Whatever the circumstances of Fesch's finding the parts, the repaired panel was sold by his descendants to Pope Pius IX, who installed it in the Pinacoteca Vaticana, now part of the Vatican Museums. The St. Jerome was once believed to have been part of the collection of the painter Angelica Kauffman, but this theory too has been rejected by recent scholars.

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