It is probable that Caravaggio was commissioned the painting of St Jerome directly by an important Italian Knight called Fra Ippolito Malaspina.

Caravaggio depicts the saint seated on his bed, writing. St Jerome is known for translating the bible from Greek into Latin. On the table is one modest volume in which he writes. Placed close to the edge of the table are a stone, a skull and a crucifix.

The coat-of-arms on the painting is that of Fra Ippolito Malaspina. It was after his death that this painting was donated to the chapel of Italy in the church of St John.