The Mass of Bolsena depicts an episode that took place in 1263 in Bolsena, near Orvieto. During the Mass celebrated by a Bohemian priest, at the moment of consecration the blood of Christ trickled from the host, staining the corporal and thus dismissing the doubts of the celebrant on transubstantiation (that is to say the changing of the substance of the bread and wine into that of the body and blood of Christ in the Eucharist). The miracle led to the establishment of the Feast of Corpus Christi [instituted by Pope Urban the IV in 1264] and the construction of the cathedral of Orvieto, to which the corporal was transferred.

Julius II (pontiff from 1503 to 1513), witnesses the miracle kneeling to the right of the altar, with cardinals Leonardo Grosso della Rovere and Raffaello Riario, Tommaso Riario and Agostino Spinola, his relatives and the chair bearers of the group.