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In this paper, we present a bioclimatic approach to (1) differentiate populations of the endemic Mexican columnar cactus Neobuxbaumia tetetzo within the Tehuacan-Cuicatlan Valley and (2) evaluate, under two possible future scenarios (years 2050 and 2080), the effects of climate change on the total species distribution in this area, as well as on groups of populations defined by their bioclimatic models. Four population groups were identified, and principal component analysis showed that the variables that explained more than 40% of the climatic variation were precipitation of the wettest quarter and temperature seasonality. Bioclimatic models under the different scenarios indicated that when the overall species distribution was analyzed, this area will probably have contracted by 19.5% by the year 2050 and 47.05% by the year 2080, whereas the separate analysis of population groups projected area contractions of 18.4% by the year 2050 and 51.95% by the year 2080. These results demonstrate the importance of exploring new approaches for evaluating and predicting current and future distribution of plant species.