The Chihuahuan Desert Region (CDR) is the largest desert area in North America, and the southeastern portions contain the richest areas in Cactaceae in the continent. This research was advocated to understand the diversity of cacti in northern Zacatecas and southern Coahuila, as well as to explore species rarity, environmental relations and conservation alternatives. A geographical square measuring a quarter degree was intensively surveyed through 50, 3-km long transects, distributed in 25, 6-minute sub-squares. The geographical square was selected because of its altitudinal and environmental heterogeneity. Cacti were identified and local rareness observed, 764 specimens were deposited at the National Herbarium of Mexico (MEXU). Specimen and locality information were captured in the Database for Cacti of Central and North America. A general evaluation of the cactus diversity (species richness), levels of endemism and rarity were performed. A total of 45 species were found, just below El Huizache, Tolimán and Mier y Noriega, with 7 new records for Zacatecas, 2 for Coahuila and 3 for both Mexican states. We found 26 endemic species from the CDR, five endemic to the Main and Meridional subregions and 21 endemic to the Main subregion, sensu Hernández. Two species are endemic to the state of Zacatecas and three species are endemic to both states. A new index for rarity (Average rarity, Ar) is presented, obtained as the mean of five variables: level of endemism, species relative frequencies, local rareness, and climatic and edaphic (soil) specialization. Rabinowitz rarity (1981) was calculated for all species and transformed into numerical values to compare it with the obtained Ar values. There are 26 rare species following Rabinowitz and 16 rare species following Ar (≥0.5). Ar values resulted smooth and with a higher explanation power (r^2). Just five species resulted with a Rabinowitz rarity of 7 (transformed R of 1) and Ar (≥0.82). A general complementarity analysis was used to address conservation in the studied area, which was enhanced with other four complementarity analyses, including our Ar. Nine sub-squares were found relevant for cacti protection. Soil types and a complete climatic analysis from original data were used to search for environmental relations through Principal Component Analyses. The main preferences for climatic variables and anomalies are highlighted. The Ar index is an adequate tool for measuring species rarity and presents it in a balanced and smooth way, not just fixed Rabinowitz categories, allowing the understanding that some species might be rare in different ways in different areas and environmental conditions, something that seems to occur in cacti. Further research is encouraged on Ar for comparisons and even mapping, as well as for Natural Protected Areas (NPA) design.