The species Mentzelia thompsonii Glad was published in 1976 based solely on herbarium material, and it is the only species in Mentzelia section Trachyphytum that has not been examined cytogenetically. Here we report that M. thompsonii is diploid (2n  =  18), making it the easternmost diploid species in section Trachyphytum and the only one that does not occur in California. The diploid status and edaphic specialization of M. thompsonii suggest that it is a paleoendemic isolated from other diploids in Trachyphytum by specialization during Pleistocene climate change. Our investigations have also uncovered confusion in the literature and herbaria regarding the taxonomy of M. thompsonii and its overall place within Mentzelia. Mentzelia thompsonii has been synonymized with Mentzelia humilis (Urb. & Gilg) J. Darl. (a member of section Bartonia) in several prominent databases and herbaria. To the contrary, our studies reveal that M. thompsonii is distinct from M. humilis; furthermore, as a unique component of Colorado Plateau diversity, it is critical for inferences of biogeographic evolution in section Trachyphytum.