Saint Jerome sits at a small pedestal desk within a niche, apparently writing in a book that he supports with his left hand. Casting a deep shadow over the right side of Jerome's body and the back of the niche, the hatching hints at the depth of the shallow space. Although by the mid-1600s this depiction was considered a little old-fashioned, artists in the Renaissance frequently showed the intellectual saint at work in his study.
Juan del Castillo changed his mind about the composition in several minor areas. He altered the saint's cap to a cardinal's hat and reduced the drapery in the lower left, part of which originally fell outside the edge of the niche, so that it would fit within the design. Although he probably intended the design for a wall decoration, it also could have been used for a painting in an arched frame.
Castillo may have drawn the figure study on the back swiftly from life or used a flayed cadaver to capture the lifeless droop of the man's body.