The so-called Madonna dei Palafrenieri di Palazzo is one of the key works in the mature artistic production of Caravaggio and obviously was the most prestigious of his Roman commissions. In point of fact, the painting, known also as Madonna del serpe, was to be placed over the altar of the Confraternity, which commissioned it, in the renovated St. Peter's Basilica in Vatican. Today this place is decorated with a mosaic depicting Archangel Michael, based on Guido Reni's altar painting at the church of Santa Maria della Concezione in Rome.

However, for unclear reasons Caravaggio's masterpiece had been rejected by the Sacred College of Cardinals and was handed over by the Parafrenieri to the Cardinal Nephew Scipione Borghese. In this way the canvas found itself in the Villa Borghese in Rome, where it can be seen today. There the cardinal had assembled his vast art collection. An avid art collector and a powerful person, he could have made use of his position as Plenipotentiary of Justice to quickly proclaim the painter subject to a pena capitale (which meant price on his head), and thus this could have been the last painting of Caravaggio. The artist was guilty of murdering Ranuccio Tomassoni of Terni in an alleged duel. Such was the outcome of a quarrel that took place at the pallacorda, or tennis court (with four men on each side), in a space still extant at Campo Marzio.

A picture painted by an assassin could not have been exhibited on an altar in the greatest church of Christianity. In the author's opinion, that is the very reason, and a not very improbable one, why the painting had been rejected. For the cardinal (due to his own sentence, condemning Caravaggio to death), it could have also been the last work done by the artist in whom he had became interested in those years (1605—1606) and whom he commissioned to paint an official portrait of his uncle pontiff (Paul V), to be later joined by the Saint Jerome Writing.

There could not have been any other reasons, since the charges against an unorthodox iconography of the painting: the "Immaculate Conception Corredentrix" in the presence of her mother, St. Anne, the patron saint of the Confraternity, are fully unfounded. This iconography had not been codified yet. Besides, equally ungrounded were accusations addressed at the painter's choice of "Lena, who is a woman of Michelangelo [Caravaggio]" as a model for Madonna. Caravaggio had already used her before, in the Madonna of the Pilgrims (Rome, Sant'Agostino) and the strict ecclesiastical commissions had nothing to object to the statuary beauty of the Mother of God, even if in the painting for St. Peter's Lena appears in radiant beauty, full of maternal carnality. Here, there was nothing to object to, unlike in the case of the Death of the Virgin (now in Louvre), painted for the church of Santa Maria della Scala and also rejected, for moral reasons. Nevertheless, it is obvious that at the base of both rejections lay, above all, the stains of blood "at the Pallacorda, in Campo Marzio" and the ensuing, eventful escape of the badly wounded Caravaggio from Rome. Lena (most probably Elena) was the person unwittingly and indirectly reputed guilty of rejection of the St. Peter's painting. The girl was courted by the notary, Mariano Pasqualone, who perhaps also had to square accounts with Caravaggio, as the painter had attacked him with a sword shortly before, in via della Scrofa. The motif is precisely known: it was Lena about whom the criminal records do not say anything but that she had connexions with the painter and that she lived with her mother "at the foot of Piazza Navona" ["in piedi a Piazza Navona"], that is to say, at the end of the square, in a house which belonged to the Consistorial advocate Sertorio Teofili (who never received any courtesans, and Lena has many times been reputed to be one).

This place has never been indicated as such by scholars. The present explanation was made possible thanks to a happy discovery of a plan of the city showing the real property in the course of being purchased by the Pamphilj family, with the intention of erecting there, on an area occupied by many smaller edifices, a palace for the family of the newly elected pope Innocent X. On that plan (preserved in the Doria Pamphilj Archives in Rome) are clearly indicated many earlier buildings, among which also that of Sertorio Teofili, which is the reason why his house, being the home of Lena, has never been identified. The "agonal lane" which sheltered the entrance to the residence, passing from Piazza Navona to the lateral Piazza di Pasquino and Via Santa Maria dell'Anima, does not exist any more, since it had been incorporated into the complex of buildings, which nowadays are housing the Gallery of Palazzo Pamphilj, frescoed by Pietro Da Cortona.