B-RAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. Mutations of B-RAF have been described in up to 100% of Hairy cell leukemia, 40-70% of Langerhans cell histiocytosis, approximately 50% of Erdheim-Chester disease, approximately 5% of diffuse large B cell lymphoma and plasma cell neoplasms and less than 5% of chronic lymphocytic leukemia. Some types of Hairy Cell Leukemia (eg, Hairy Cell Leukemia-Variant, Hairy Cell Leukemia with IgHV4-34 rearrangement) are negative for BRAF V600E mutation and may have MAP2K1 mutations. While some reports have found that 10-20% of cases of acute leukemias (ALL or AML) may have BRAF mutations, other reports have described no BRAF in those diseases or in myeloid diseases such as MDS or CML. The hotspot for mutations in BRAF is at codon Val600 and these are activating mutations. The most common activating mutation is p.Val600Glu(V600E). B-Raf inhibitors(eg, Vemurafenib) have been FDA approved for therapy for various tumor types and have been used in Hairy Cell Leukemia in some clinical settings, including in combination with other therapy.