In 1521, seven years before his death, Albrecht Dürer painted an image of Saint Jerome, currently in the National Museum of Ancient Art in Lisbon. This surprisingly under- researched painting unites themes of Melancholia, ocular misperception, subjectivity, skepticism, and a disrupted reciprocity between representational appearance and truth that characterize much Northern Renaissance art of the sixteenth century. The painting also shows how profoundly pictures of saints were drained of the holiness and comfort that characterized the era before the Lutheran Reformation. Like Albrecht Dürer's engraving, Melencolia I of 1514, the Lisbon Jerome rests his face in one hand in a posture that embodies introspection. He points to the skull with the index finger of his left hand and locks eyes with the viewer, linking his world to the beholder's. His books and pen are neglected and inert. The space is ambiguous, tight and uncertain, and draws the viewer out of the holy narrative rather than more deeply into it. Is the Christ on the left a tiny object or a larger object farther away? The green panel behind the saint is truncated and indeterminate, just like the structure behind the winged figure in Melencolia I. The space mirrors the saint's melancholic disorientation. In Dürer's other representations of Jerome, the saint exemplifies the virtues of piety and hard work. For instance, Jerome studies peacefully in the 1514 Master Engraving, or practices penance, as in the 1496 engraving of the saint in the wilderness. In contrast, in the Lisbon painting, Dürer depicts an idle, despairing man preoccupied with mortality, as his eyes plead with the viewer and his hand points wearily to the skull. As Erwin Panofsky noted long ago, the disciplined, pious scholar has evolved into a melancholic. This presentation will demonstrate the transformation of piety into melancholy as exemplified by the scholar saint Jerome.