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 8–15% of colorectal cancer (CRC) harbors BRAF mutations. BRAF G469A mutation in exon 11 is infrequent in CRC and occurs within the kinase domain. The presence of BRAF mutation is significantly associated with right-sided colon cancers and is associated with decreased overall survival. BRAF mutation in a microsatellite unstable colorectal carcinoma indicates that the tumor is probably sporadic and not associated with Lynch syndrome (HNPCC). However, if a BRAF mutation is not detected, the tumor may either be sporadic or Lynch syndrome associated. Detection of BRAF mutations may also be useful in determining patient eligibility for anti-EGFR treatment. Some studies have reported that patients with metastatic CRC (mCRC) that harbor BRAF mutations do not respond to anti-EGFR antibody agents (cetuximab or panitumumab) in the chemotherapy-refractory setting. Results should be interpreted in conjunction with other laboratory and clinical findings.