Abstract: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of pulmonary malignant tumors, accounting for only 2.1%-3.5% of all pulmonary malignant tumors. The diagnosis of LCNEC is challenging, especially on small biopsy or cytological samples. Due to limited clinical data, the optimal treatment for LCNEC remains unclear. Recent studies have indicated that LCNEC shave a unique molecular profile and can be further divided into two subtypes:RB1-mutant and RB1-wild type. Patients with RB1-wild type LCNECs showed significant longer overall survival (OS) on treatment with non-small cell lung cancer-related regimens than with small cell lung cancer-related regimens. However, different regimens showed similar effects on RB1-mutant LCNECs. Previously, only retrospective studies and case reports have focused on targeted therapy or immunotherapy against LCNEC. Herein, This article will review the progress of molecular typing and clinical treatment of LCNEC.