BACKGROUND/AIM: Human papillomavirus-positive (HPV+) tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC) have better outcome than corresponding HPV- cancers. To better individualize treatment, additional predictive markers are needed. Previously, we have shown that mutated fibroblast growth factor receptor 3 protein (FGFR3) was correlated to poorer prognosis and here FGFR3 expression was further analyzed. PATIENTS AND METHODS: One-hundred-fifteen HPV+TSCC/ BOTSCC biopsies were analyzed for FGFR3 by immunohistochemistry (IHC), and 109/115 were analyzed for FGFR3 mutations by Ion Proton sequencing, or by Competitive Allele-Specific Taqman PCR (CAST-PCR). Disease-free survival (DFS) was then calculated according to FGFR3 IHC expression. RESULTS: CAST-PCR was useful for detecting the three most common FGFR3 mutations. Focusing especially on the 98/115 patients with HPV+TSCC/BOTSCC and wild-type FGFR3, high FGFR3 expression correlated to significantly better 3-year DFS, p=0.043. CONCLUSION: In patients with HPV+TSCC/BOTSCC and wild-type FGFR3, overexpression of FGFR3 was correlated with better DFS.