In 1912, 68 medieval crania were excavated from a cave at Safed in the eastern Mediterranean and brought to the United Kingdom. It is only recently that these skulls have been studied for evidence of disease. One adult individual demonstrates multiple lesions of the cranial vault, compatible with treponematosis. Radiocarbon dating suggests the year of death to be between 1290–1420 AD. This range equates to the mamluk period, just after the crusades. This is the oldest dated case of treponematosis in the Middle East, and the first to confirm its presence there before the epidemiologically important transatlantic voyage of Christopher Columbus. The finding has significant implications for our understanding of the introduction of the disease to the Middle East and of the medieval diagnosis of ulcerating skin conditions by medical practitioners in the Mediterranean world. Am J Phys Anthropol 121:000–000, 2003. © 2003 Wiley-Liss, Inc.