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Background: Ameloblastoma is an aggressively growing, highly recurrent odontogenic jaw tumor. Its association with BRAFV600E mutation is an indication for BRAFV00E‐inhibitor therapy The study objective was to identify a sensitive low‐cost test for BRAFV600E‐positive ameloblastoma. We hypothesized that immunohistochemical staining of formalin‐fixed paraffin‐embedded tissues for BRAFV600E mutation is a low‐cost surrogate for BRAFV600E gene sequencing when laboratory resources are inadequate for molecular testing. Methods: Tissues from 40 ameloblastoma samples were retrieved from either formalin‐fixed paraffin‐embedded blocks, RNAlater™ stabilization solution or samples inadvertently pre‐fixed in formalin before transfer to RNAlater™. BRAFV600E mutation was assessed by Direct Sanger sequencing, Amplification Refractory Mutation System‐PCR and immunohistochemistry (IHC). Results: BRAFV600E mutation was detected by IHC, Amplification Refractory Mutation System‐PCR and Direct Sanger sequencing in 93.33%, 52.5% and 30% of samples respectively. Considering Direct Sanger sequencing as standard BRAFV600E detection method, there was significant difference between the three detection methods (휒2 (2) = 31.34, p < 0.0001). Sensitivity and specificity of IHC were 0.8 (95% CI: 0.64–0.90) and 0.9 (95% CI: 0.75–0.99) respectively, while positive predictive value and negative predictive value (NPV) were 0.9 and 0.8 (Fischer's test, p < 0.0001) respectively. Sensitivity and specificity of Amplification Refractory Mutation System‐PCR detection method were 0.7 (95% CI: 0.53–0.80) and 0.9 (95% CI = 0.67–0.98) respectively, while PPV and NPV were 0.9 and 0.6 respectively (Fischer's test, p < 0.0001). Conclusion: Low‐cost and less vulnerability of IHC to tissue quality make it a viable surrogate test for BRAFV600E detection in ameloblastoma. Sequential dual IHC and molecular testing for BRAFV600E will reduce equivocal results that could exclude some patients from BRAFV600E‐inhibitor therapies. [ABSTRACT FROM AUTHOR]