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The distribution of cacti species that inhabit the Sierra Madre Oriental (SMO) was analysed. Grid-cells were analysed using parsimony analysis of endemicity (PAE) and endemism indices. Areas characterized by their diagnostic species were determined, aiming to propose areas for the conservation of threatened cacti. Distributional data were obtained from 1936 herbarium specimens, electronic information, and from field collections. Eight areas of endemism and three main clades were obtained from the grid-cell analysis. Areas obtained from the endemism indices are very similar to those obtained with the PAE, but differ in the association of grid-cells. PAE showed endemism patterns indicating that southern and central sections of the SMO province are the areas richest in geographically-restricted species. The results obtained with different endemism indices detected more or less the same areas, although the importance level is different. The corrected weighted endemism index can be considered as a reliable measure of endemism because it is unrelated to species richness. A regionalization of the SMO in three subprovinces is suggested, supported by characteristic cacti taxa and the existence of natural barriers. (C) 2009 The Linnean Society of London, Biological Journal of the Linnean Society, 2009, 97, 373-389.