The League, commanded by Francesco II Gonzaga, Marquess of Mantua, was made up of numerous nation-states determined to prevent French dominance in Italy, and included the Holy Roman Empire, Spain, Venice, Milan, and the Papal States controlled by Pope Alexander VI.

[3] During Francesco's absence from Mantua, Daniele da Norsa, a Jewish banker, had purchased a house in the city's San Simone quarter and replaced the image of the Virgin Mary which decorated its façade with his own coat of arms.

The presence of a sulphur-crested cockatoo in the painting is considered as evidence of Arab trade in the Australasian region which dates all the way to when one such bird was gifted from Sultan al-Kamil to Frederick II in the 1240s.

The base of the throne, with lion paws, has, within a medallion, the inscription "REGINA/CELI LET./ALLELVIA" (Queen of Heaven, rejoice, Alleluia); it lies on a circular basement with a bas-relief of the "Original Sin" and other stories from the Book of Genesis which are partly obscured by the praying figures.

Opposite to the donor are St. John the Baptist with a cross featuring the usual cartouche saying "ECCE/AGNVS/DEI ECCE/Q[VI] TOLL/IT P[ECCATA] M[VNDI]" (Behold the Lamb of God, which takes away the sins of the world), and his mother, St. Elizabeth, protector of Isabella d'Este, wife of Francesco Gonzaga.