[1] The main subject of this painting is St. Jerome, who is the thin central figure depicted kneeling with the red cloth.

[4] In 1620, Giovanni Lanfranco accused Domenichino of stealing ideas from Agostino Carracci's painting of the same subject matter.

The Last Communion of St. Jerome was a subject painted rarely at this time, which added more leverage to Lanfranco's charge of theft.

In Passeri's defense for Domenichino, he claimed that it was hard to avoid the example set by Carracci's painting of the central figures of Jerome receiving communion from the priest and that Agostino's central image of St. Jerome was so definitive that Domenichino had no alternative way of envisioning the scene without including the inspiration from Agostino's version.

Passeri continued by stating that Domenichino did what he could to vary from Carracci's version, by changing the secondary figures, composition, and other details in his own interpretation.

[7] Elements in Domenichino's version that are similar to Carracci's are the use of flying putti, the large candlesticks, and the main figure of St. Jerome.

Domenichino's figure of St. Jerome is almost identical to Agostino's, except for mirroring the placement and changing the pose to open arms.

Domenichino has it loosely hanging off St. Jerome's' shoulders, as if it's about to fall off him and revealing white fabric wrapped around his waist.

The Italian scholar Carlo Cesare Malvasia (1616–1693) responded to Domenichino's notoriety and artists in general by writing, "What painter does not steal in some way?

Either from prints, or reliefs, or nature herself, or from the works of others, turning the poses in the opposite sense, twisting an arm more, showing a leg, changing the face, adding a drapery, and, in short, judiciously hiding the theft?