Raphael's Deposition was painted for Atalanta Baglioni in memory of her son Grifonetto, who was killed in the fighting for the dominance of Perugia, and housed in the church of S.Francesco in Perugia in 1507. It remained there for 101 years, until it was removed at night with the complicity of the priest and sent to Pope Paul V, who gave it to his nephew for his collection and it thus became the property of the Borghese family. After the Treaty of Tolentino the painting was sent to Paris in 1797. When it came back to Rome in 1816, only the central scene was returned to the Borghese collection, while the three theological virtues, Faith, Hope and Charity, remained in the Vatican Museums (the ornamentation surmounting it by Tiberio Alfani is in the National Gallery of Umbria).

This large altarpiece presents the scene like a Roman relief and is inspired by the reliefs on ancient Roman sarcophagi depicting the transportation of Meleager. It is interesting to note that in his preliminary sketch the artist has drawn Christ lying in the ground, as in the painting by Perugino, but when he executed the painting he decided on the antique form of transportation, as seen in a relief he probably studied on the Montalvo sarcophagus in Florence (now in the Torno Collection, Milan). But the influence of Michelangelo can also be seen in the composition of Christ (cf. the Pietà, St.Peter's) and the figure seen in the profile supporting the Madonna repeats a similar pose in the Doni Tondo (in the Uffizi, completed a year before the Deposition).