Treatment responses of BRAF mutant melanoma to BRAF inhibitors are often limited by the development of resistance. This case report describes the use of multiplatform molecular profiling in sequential surgical samples of a treatment-resistant tumour site subjected to ongoing treatment with dabrafenib in a patient with metastatic cutaneous BRAF mutant melanoma. Next-generation sequencing showed the presence of the V600E, fibroblast growth factor receptor 2 (FGFR2), phosphatase and tensin homologue (PTEN) and p53 gene mutations. With a continuous presence of the BRAF V600E, FGFR2 and PTEN mutations and appearances of new mutations in the PTEN gene at R137H and T321fs and p53 R273C genes during ongoing treatment, this case report indicates intratumoural clonal evolution as a resistance mechanism. Two new mutations, the G542E exon 12 mutation variant of the FGFR2 gene and the R273C mutation variant of the p53 gene, are reported for the first time in BRAF mutant melanoma.