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As the number of cancer survivors grows, so does the number of co-occurring primary malignancies and secondary malignancies. In rare cases, single driver mutations can be responsible for concomitant primary malignancies. By understanding the mechanisms that drive multiple primary malignancies (MPM), clinicians are capable of targeting molecular pathways that drive oncogenesis resulting in the successful treatment of many malignancies while also reducing the side effects of conventional chemotherapy.  Herein, we report a case of co-occurring hairy cell leukemia (HCL) and malignant melanoma in a 69-year-old male. This patient tested positive for the BRAF V600E mutation and was initiated on a single agent, vemurafenib. He, unfortunately, succumbed to his illness before completion of his planned therapy course.   This case report is intended to highlight the rare co-occurrence of BRAF-positive HCL and melanoma and to encourage driver mutation evaluation when a patient presents with MPM and the possibility of a unifying driver mutation. To the best of our knowledge, this is the first case of a co-occurring BRAF positive melanoma and HCL to be reported in a chemotherapy-naïve patient.

BRAF V600E Mutation in Multiple Primary Malignancies: A Hairy Affair