Hyperostosis frontalis interna (HFI) is a disease characterized by excess bone growth on the internal lamina of the frontal bone and, occasionally, other cranial bones. Although the disease is fairly common in modern populations, its etiology is poorly understood. Hyperostosis frontalis interna has been identified in antiquity, primarily in the Old World, but with a much lower frequency than in modern groups. The purpose of the present study is to report multiple cases of HFI at Pueblo Bonito (Chaco Canyon, New Mexico). Twelve out of 37 adults with observable frontal bones exhibited HFI, ranging from mild to severe, including 11 females and one male. This is the first published case report of HFI in archaeological remains from the New World having a frequency comparable with modern groups. Most archaeological cases of HFI are isolated, so comparative data for multiple cases at one site are rare. The results of this study emphasize the importance of looking for HFI in archaeological remains, although it is rarely observed. Possible genetic and environmental factors for the high frequency of HFI at Chaco Canyon are considered, but additional research is needed to discover the etiology and to better understand why HFI sometimes occurs at modern frequencies in ancient populations. Am J Phys Anthropol, 2006. © 2006 Wiley-Liss, Inc.