BRAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. Approximately 10% of cutaneous squamous cell carcinomas harbor somatic mutations in BRAF. The G469A mutation in exon 11 results in an amino acid substitution at position 469 in BRAF, which occurs in the highly conserved motif of the kinase domain. Most mutant BRAF proteins, such as G469A, have increased kinase activity and are transforming in vitro. Though BRAF mutations and targeted therapies have been have been studied in other solid tumors, the predicative and prognostic significant in cutaneous squamous cell carcinoma is unclear and needs to be further investigated.