In the main painting of the altarpiece, Saint Jerome is on a panel in the centre. To either side are saints connected with him: Pope Damasus and Saint Eusebius on the left, and Saint Paula with a book and Saint Eustochium with a lily on the right. In the foreground, either side of the panel with Saint Jerome, two donors kneel, possibly Gerolamo di Piero di Cardinale Rucellai (died 1497?) and his son.
Four more scenes are illustrated on the predella, or lower section of the altarpiece.