An analysis of the current and historical literature is presented in order to assess the weight of evidence for the existence of tuberculosis among the Native Americans of North America before the time of Columbus. Literature related to pertinent artifacts, biologic specimens, geographic and geologic history, epidemiology, and early travelogues and histories in considered. While the evidence does not convincingly confirm or deny the presence of this disease in America's earliest human history, an understanding of the factors related to the epidemiology of tuberculosis is of value for both social and public health reasons.