Saint Jerome is on a panel in the centre. To either side are Saints Damasus (as Pope), Eusebius, Paula and Eustochium (with a lily). Two donors, possibly father and son, kneel at prayer in the foreground. The father may be Gerolamo di Piero di Cardinale Rucellai (died 1497?), whose tomb is near where the picture hung.
The altarpiece was almost certainly painted for the church of the Hermits of Saint Jerome (S. Gerolamo) of Fiesole at Fiesole. The predella has the Rucellai arms at each end and four narrative scenes: Jerome taking the thorn out of the lion's paw; his vision that he was beaten for still enjoying pagan literature; his death; and his appearance with Saint John the Baptist to Saint Augustine.
The frame appears to be the original one, but extensively remade and regilded in about 1850. The back of the altarpiece has a monogram that is probably a panel-maker's stamp.