Amazonia is a highly threatened rainforest that encompasses a major proportion of Earth's biological diversity. Our main goal was to establish conservation priorities for Amazonia's areas of endemism on the basis of measures of evolutionary distinctiveness. We considered two previously identified sets of areas of endemism. The first set consisted of eight large areas used traditionally in biogeographical studies: Belém, Tapajós, Xingu, Guiana, Rondônia, Imeri, Inambari, and Napo. The second set consisted of 16 smaller areas that were subdivisions of the larger areas. We assembled a data set of 50 phylogenies that represented 16 orders and 1715 distributional records. We identified priority conservation areas for the areas of endemism according to node-based metrics of evolutionary distinctiveness. We contrasted these results with priority areas identified on the basis of raw species richness and species endemicity. For the larger areas, we identified Guiana and Inambari as the first- and second-most important areas for conservation. The remaining areas in this first group scored half (e.g., Napo) or less than Guiana and Inambari on all indices. For the smaller areas, a subdivision of Guiana (i.e., Guyana and the Brazilian states of Roraima and Amazonas) was at the top of the ranking and was followed by a subdivision of Inambari (i.e., northwestern portion of Amazonas) and then another subdivision of Guiana (i.e., Suriname, French Guiana, and the Brazilian state of Amapá). The distinctiveness-based rankings of the priority of areas correlated directly with those derived from species richness and species endemicity. Current conservation strategies in Amazonia, although they rely on many other criteria apart from phylogeny, are focusing on the most important areas for conservation we identified here. © 2010 Society for Conservation Biology.