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It is well established that fibrous dysplasia (FD) is caused by mutations of the Arg201 codon of the GNAS gene. However, the role of GNAS mutation in the pathogenesis of cement-osseous dysplasias (COD) and cemento-ossifying fibromas (COF) is not fully known. In this study, we examined COD and COF for mutations at the Arg201 codon of the GNAS gene.The study sample included formalin-fixed, paraffin-embedded tissue blocks from 8 COF and 24 COD. We used 2 PCR-RFLP methods to detect mutations at the Arg201 codon of the GNAS gene.Mutations at the Arg201 codon of the GNAS gene were not present in any of the COD and COF examined.GNAS mutations do not play a role in the pathogenesis of COD and COF. This highlights a clear molecular distinction between FD and other histologically similar fibro-osseous lesions of the jaws.