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In the last decades research efforts studying Amazonian biodiversity have increased substantially, with many new localities surveyed, new specimens collected, and some new regional collections established. In our study, we revised, updated, and summarized the available data on the diversity, distribution, species richness, and conservation status of lizards from the Brazilian Amazonia. We recorded 138 species-level taxa of lizards in the Brazilian Amazonia that presented five general patterns of distribution, plus some cases of unique distributions. Species richness is unevenly distributed across the region, varying between one and 44 species in a single grid, with 37–44 species in the richest areas. Based on the overlap of occurrence area of each species with protected areas (strict nature reserves; managed resource protected areas; protected indigenous peoples’ territories) and deforested layers, we show that 58% of the analyzed species (n = 75) present more than 50% of their occurrence area outside of any protected area, and 20% (n = 26) of them present 33% or less occurrence in protected areas. Strict nature reserves (strictly protected areas) are responsible for the main protection (≥50% of the protected area) of only 3% of the species (n = 4). Indigenous peoples’ territories represent the main protection area for 31% of the species (n = 40). Ten species present more than 50% of their occurrence in area deforested, and for 12 species the range varied between 33 and 50% of habitat loss. Revising the International Union for Conservation of Nature conservation status categories for a regional assessment, three species were classified as EN (Endangered), six as VU (Vulnerable), and 15 as NT (Near Threatened). Species with occurrence in Southern Amazonia are the most threatened. We presented the core areas for conservation of species richness and discussed their conservation status. Habitat loss due to mechanized agriculture (mainly from soy plantation), pastures, fire, and infrastructure project (e.g. roads and hydroelectric dams) are the main threats to the lizard fauna. Southern Amazonia is the region with the highest human pressure and, at the same time, it is the least protected. We suggest a revision to the mosaic of interconnected conservation areas, mainly in Southern Amazonia, and recommend that new infrastructure projects in the region take preventive actions to mitigate the direct and indirect impacts on the local lizard fauna. [ABSTRACT FROM PUBLISHER]