A second theory argues that the work was intended for Federico's mother Isabella d'Este, who wanted a nocturnal scene.

[2] Saint Jerome is depicted as a hermit in the desert, engaged in penance, beating his chest with a stone while addressing a prayer to the crucifix hanging on a stick at the top right.

Behind him is the inevitable tamed lion and the cardinal's hat, as well as the book of the Vulgata.

Compared to the previous representations of the subject, Titian renewed the pathos of the scene with an innovative lighting, which highlights some details while leaving in the shade some less significant, but still necessary in the iconography.

In the landscape, a luminous source in the distance creates innovative effects of prominence, giving the grove a restless and mysterious atmosphere.