English: Vasari may have painted this biblical scene as well as three others (Walters 37.1705, 37.1176, 37.1704) in brown monochrome as a study for related compositions in a series of 18 larger, multicolor panels representing the correspondences between the Old and New Testaments made in 1545-1546 for the sacristy of the church of San Giovanni a Carbonara in Naples. Vasari's skill with the pen comes out in the preliminary drawings, visible in The Fall of Manna, to which he added layers of paint with his brush and fingers.

These particular subjects relate to the establishment of the Holy Eucharist (Communion), when the priest at the altar symbolically re-enacts the sacrifice of Christ. The Last Supper depicts the institution of the Holy Eucharist by Christ when he offers bread and wine to his disciples, describing their symbolic significance as his body and blood, which he offers for their salvation.

The three episodes from Genesis and Exodus foreshadow Christ's sacrifice or the role of bread as sustenance and as an offering. In The Sacrifice of Isaac, Abraham is ordered by God to sacrifice his son Isaac and is then prevented from doing so by an angel. In The Meeting of Abraham and Melchizedek, Abraham returns from battle having freed his brother from the enemy and is met by the high priest Melchizedek, who offers him bread and wine. In The Fall of Manna, God provides food for the starving Israelites in the desert.