Saint Jerome (about 342 - 420), the chief inspiration for Christian penitents and hermits, is shown on the left with a crucifix. Saint Nicholas of Tolentino (about 1245 - 1305) wears the black habit of the Augustinian order and holds lilies over his breast, which glows with sacred radiance. The coffin on which Christ stands is most unusual and may be taken to refer to his future conquest over death.
This work was painted towards the end of the period that Lotto spent mainly in Bergamo. There is another, better preserved, version of the picture (apparently painted at the same time but drawn first), in the Museum of Fine Arts, Boston.