Pulmonary mucoepidermoid carcinoma (MEC) is a rare form of lung cancer that originates from submucosal glands of tracheobronchial tree. Unlike low-grade tumor with benign nature, high-grade case is even rarer and has aggressive clinical features with no definite treatment option. Here, we report a case of high-grade pulmonary MEC with fulminant clinical course. A 74-year-old man presented with cough, sputum and mental change. Chest imaging showed massive mediastinal lymphadenopathy with obstructive pneumonia, and multiple metastases in lung and adrenal gland. Bronchoscopy showed polypoid masses obstructing right main bronchus and bronchus intermedius. Histopathology revealed a mixture of glandular structure lined with mucussecreting cells and nests of squamoid cells with nuclear atypia and pleomorphism, which is compatible with high-grade MEC. We intensively treated the patient with combination antibiotics and ventilator care. However, the patient did not respond to the treatment and rapidly deteriorated, and finally expired a month after diagnosis.