Large cell neuroendocrine carcinoma (LCNEC) is a poorly differentiated high-grade neuroendocrine tumor with very aggressive behavior. Herein, we report a 74-year-old male smoker who initially presented with a symptomatic metastatic brain tumor of unknown origin (MBUO). Primary pulmonary LCNEC was not diagnosed until 3 years later. Both the metastatic brain tumor and the primary lung cancer were successfully treated by surgical intervention, and the patient had a very favorable outcome. Management of MBUO should be aggressive if patients have only isolated brain metastasis. Periodic re-evaluation after treatment of the brain tumor may help to detect an earlier stage of primary cancer and may result in a better outcome, even in highly aggressive malignancies like LCNEC.
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