BRAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. BRAF mutations are infrequent in small intestinal adenocarcinoma, ranging from 1% to 13% of reported cases. D594 is a highly conserved residue within the kinase domain of BRAF and mutation of this residue appears to result in kinase inactivation. In vitro study has shown that kinase-dead BRAF forms a constitutive complex with CRAF in the presence of activated RAS leading to MEK and ERK signaling. The predictive and prognostic significance of this specific BRAF mutation in small intestinal adenocarcinoma needs further study. Results should be interpreted in conjunction with other laboratory and clinical findings.