The original work was commissioned by Cardinal Giulio de Medici in 1516 for the cathedral of Narbonne. The Prelate also commissioned Sebastiano del Piombo to paint a Resurrection of Lazarus for the same location, which led to competition between the two artists. Giulio kept Raphael's work and commissioned Giovanni Francesco Penni to make a copy, which he took to Naples.

The Transfiguration is Raphael's most ambitious altar painting. It even includes an episode which is not part of this biblical passage: the Apostle's failure to exorcise a possessed man. This allowed the painter to undertake an exhibition of physical and emotional states intended to surpass those depicted by Piombo.

The present copy differs from Raphael's original, not only in quality, but also in specific details. Christ, Elias and Moses appear enveloped in an aura and the trees on the left have disappeared. There is also a notable attenuation of the chiaroscuro.

In the mid seventeenth century, the Duke of Medina de las Torres acquired this painting. His son later ceded it to the Carmelite nuns of Saint Theresa in Madrid.