An S249C mutation in fibroblast growth factor receptor 3 (FGFR3) gene was recently identified in patients with cervical carcinomas (CC). However, its importance in cervical tumorigenesis is still inconclusive. Apart from CC, nasopharyngeal carcinoma (NPC) is the other major virus associated squamous cell carcinoma. We sought to clarify the frequency of the FGFR3 S249C mutation in 75 primary CC in the Thai population and to determine its prevalence in 69 primary NPC by PCR and restriction enzyme digestion. None of the patients but one NPC showed the enzyme digestion pattern consistent with the mutation. This is the first report demonstrating the role of FGFR3 in the development of human NPC. This study confirms the low frequency of the FGFR3 S249C mutation in CC. Nevertheless, the discovery of the mutation, not only in CC as reported by previous studies, but in NPC based on this report, suggests that FGFR3 may play a significant role in human CC and NPC development.