Background: Activating BRAF V600 mutations have been shown to occur in 40%–60% of melanomas, although the mutation rate among the Irish melanoma population has been reported to be lower (30%). The current standard for determining BRAF mutation status is with the use of the Cobas 4800 PCR test. IHC analysis to determine BRAF mutation status has been made possible by the development of monoclonal antibodies directed at mutant BRAF protein expression, which may be of use as an alternative to molecular testing. Methods: We identified 132 patients with metastatic melanoma between 2011 and 2014 at our institution that had tumour tested for BRAF mutation using PCR. Of these, 122 cases were suitable for IHC. Tissue samples were obtained and tested with the BRAF V600E antibody. IHC was assessed as 0 (negative), 1, 2 or 3 based on intensity of cytoplasmic staining. We assessed the incidence of BRAF mutation, investigated the sensitivity and specificity of the BRAF V600E antibody in detecting the presence of the BRAF V600E mutation. Clinical response to BRAF inhibitor therapy as per RECIST was correlated to BRAF mutation status by PCR and to IHC expression. Results: The incidence of BRAF mutation as assessed by PCR was 28.8% (38/132). The antibody showed a sensitivity of 86.1% with a specificity of 96.9%. The positive predictive value was 96.9%; the negative predictive value was 94.4%. The concordance rate between PCR and IHC was 95.1% (116/122). One false positive case and five false negative cases were observed. The results of clinical outcomes for the PCR positive cohort and the IHC level of expression cohorts are shown in the table. Conclusions: The high concordance rate of PCR and IHC methods in determining BRAF status and predicting response to therapy suggests that antibody testing is a viable and cost effective alternative to PCR testing. The BRAF V600E antibody may be suitable as a screening test for the BRAF mutation, with all negative cases being submitted for PCR testing to identify variant BRAF mutations not detected by IHC.