The religious artwork, on display at the Gallerie dell’Accademia in Venice, depicts an apparition of St Jerome in conversation with a man who may have donated money to the saint's shrine. Donating money to shrines, a common practice in Catholic Europe during the Late Medieval and Early Modern period, was believed to persuade the saint to intercede on behalf of the donor's soul. It is likely that the donor in the painting, identified as Gerolamo Amadi, commissioned the painting to remind himself of his association with St Jerome and to inform others of the relationship between the saint and himself.

The year in which the painting, measuring 40 cm by 42 cm, was executed it unknown but some art historians believe that the artwork was completed in 1451. Francesca, born in 1415 in the Republic of Florence, had entered the mature stage of his artistic career at the time in which he created the painting and may have been living in Rimini at the time. The hills in the background, standing before a blue sky that is streaked with smudges of golden-brown cloud, could represent the highland terrain around Rimini while the white buildings in the middle-distance could depict the city itself. The saint and the donor, the former located to left of the panel and the latter situated on the right, occupy an elevated position at the foreground of the painting.

St Jerome, sporting a grey beard and a bald pate, is sitting on stone bench and leafing through an open book while the donor is kneeling and holding his outstretched palms together in prayer. The saint, fixing the donor with an intense gaze, is wearing white garments that reach down to his knees while the donor is dressed in a red gown that spills out onto the floor. Neither man is speaking yet St Jerome, a renowned scholar and theologian during his lifetime, appears to be instructing the donor in matters of the faith. A young tree, it's leaves thick with foliage, is situated behind the donor while a crucifix stands on a tree stump that is located in the bottom left-hand corner of the panel.