Pottery Mound is a large Ancestral Puebloan site situated within the Middle Rio Grande (MRG) region of New Mexico. This article adds to our understanding of relationships between Pottery Mound, the Western Pueblos, and Mexico through use of biological distance analysis based on dental nonmetric traits. Extensive material and cultural influences, as well as migration events from Western Pueblos to Pottery Mound, have been proposed by several scholars, while others have highlighted parallels to Mexico, especially Paquimé. A total of 1,528 individuals from the U.S. Southwest and Mexico were used to examine relationships between Pottery Mound and these areas. We find no evidence of close biological similarity between Pottery Mound and the Western Pueblos or northern Mexico. Instead, the results indicate biological affinity between Pottery Mound and sites in the MRG region and Mogollon areas. This similarity suggests that although there is evidence for trade between Pottery Mound and other sites in the southwestern United States and Mesoamerica, trade may not have been accompanied by significant gene flow from those areas from which the trade goods originated. It is possible that neighboring regions, such as the Mogollon, served as intermediaries for trade between Pottery Mound and distant regions.