The work was commissioned in 1511 by Sigismondo de' Conti for the high altar of the church of S. Maria in Aracoeli in Rome. From here it passed in 1565 to the church of S. Anna at the Monastery of the Contesse in Foligno and, after its return from France, where it had been transferred in 1797 following the Treaty of Tolentino, it entered the collection of the Vatican Pinacoteca (1816).
Sigismondo de' Conti, a distinguished humanist of Foligno, is shown kneeling in prayer on the right: St Jerome, in the vestments of a cardinal, presents him to the Virgin, who is seated in glory with the Child Jesus. On the left St John the Baptist, dressed in animal skins, indicates the heavenly vision. Kneeling before this is St Francis, patron of the Minors, to whose church the picture was painted.
The painting was ordered by Sigismondo de' Conti out of thanksgiving to the Virgin for having saved his house in Foligno, that had been struck by lightning. The episode is recalled in the splendid landscape insertion in the background. The small angel in the centre of the composition holds a plaque without an inscription which was probably destined to recall the wish fulfilled by the Virgin.
The painting can be dated to between 1511 and 1512, in the period when Raphael was working in the Room of Heliodorus in the Vatican (Julius II's apartment).