The BRAF gene encodes a protein-serine/threonine kinase that participates in the MAPK cascade, which regulates a large variety of cell processes. Activating mutations in BRAF are found in many tumor types, including malignant melanoma, thyroid, colorectal, and ovarian carcinomas, lung adenocarcinoma, as well as in some sarcomas and gliomas. These mutations lead to constitutive activation of BRAF thereby promoting tumorigenesis. Copy number gains of mutated and non-mutated BRAF have been identified in malignant melanoma (MM), follicular thyroid tumors, astrocytoma, colorectal, and prostate cancer due to amplification of the gene or polysomy of chromosome 7. These amplifications lead to an overexpression of BRAF and to constitutive activation of the MAPK signaling pathway. Follicular carcinomas with BRAF copy number gain were observed to be more often invasive. Colorectal carcinoma or melanoma patients with BRAF V600E mutation were found to acquire resistance to MEK and BRAF inhibitors through amplification of the mutated BRAF gene. Hence, detection of BRAF amplifications in situ Hybridization may be of therapeutic relevance for these cancer patients.