Lung tumors with combined histological pattern are seldom seen exhibiting a more aggressive clinicopathological picture than tumors with a single histology. Herein, we present a 58-year-old male with mixed squamous and large-cell lung carcinoma. The patient was initially diagnosed through fluoroscopy-guided transbronchial lung biopsy with large-cell lung carcinoma of the left upper lobe. He received neo-adjuvant chemotherapy and then underwent left upper lobectomy. Postoperative pathological diagnosis was combined squamous and large-cell neuroendocrine carcinoma. Two months after surgery, restaging revealed brain metastatic deposits. Local radiotherapy was promptly applied with relatively good response and the patient is under observation eight months after diagnosis. A brief review of the current literature is also included with special emphasis on the clinicopathologic aspects and prognosis of lung tumors with mixed histology.