The damaged Deposition from the Cross of 1517 by Pietro Vannucci known as Perugino, is one of the high points of his artistic production, dating to a few years of his death. Here the master also looks to the pathos of Raphael, his former pupil, now on his way to immortal fame. In fact, Christ shows many similarities to the Urbino artist's work. The episode of Mary's fainting, echoing the similar subject depicted by Giotto in the basilica of St. Francis in Assisi, underscores how Perugino continues to make himself an interpreter of that typically Umbrian world of lauds, which have their roots in the medieval period.

The master depicts the scene in his highly original vision of extreme formal synthesis, almost impressionistic, in the quick touches of the landscape, while at the same time emphasizing the drama of the event. The fresco, hidden in a cavity wall, was rediscovered in 1834 by the German Antoine Remboux. After him the fresco impressed numerous painters including the Nazarenes, Purists, and Preraphaelites, who understood it as a source of inspiration for their Romantic sensibilities.