Saint Onuphrius is perhaps the least known of the hermit saints. The son of the late fourth-century King of Syria, Onuphrius renounced the throne to live as a hermit in the desert near Thebes. As in the present painting, he typically appears in a rocky landscape dressed only in his long grey hair. The golden crown and scepter at his feet symbolize the discarded trappings of earthly power; his withdrawal from the world is emphasized by the birds that, according to legend, kept him alive in the desert for over seventy years. Onuphrius was particularly popular in the Middle Ages as the patron saint of weavers (due to the abundance of his hair). He is also central to the iconography of the 'wild man', the primitive man of the forest who symbolized lust and aggression and appeared at the fringes of society, particularly in Northern prints of the fifteenth and sixteenth-centuries.
While the attribution of this painting is uncertain, Saint Onuphrius in the Wilderness shares certain characteristics with the paintings of Dosso Dossi, particularly those executed during the last decade of his life. The drama of the densely wooded landscape that opens onto a vista at one side is reminiscent of such works as Travelers in a Wood (Besançon, Musée des Beaux-Arts) especially in the scale of the figure with respect to the landscape and in the looseness of the brushwork in the foliage. The unusual formation of the rock face at the left reflects Dosso's interest late in his career in Netherlandish landscape painters such as Joachim Patinir. The choice of St. Onuphrius from the pantheon of hermit saints popular around this time is, furthermore, in keeping with Dosso's penchant for unusual subject matter.