Large cell neuroendocrine carcinoma (LCNEC) is a newly recognized clinicopathologic entity. The clinical features of advanced LCNEC are still unclear, because most of the previous reports have described resected cases. The aim of this study was to clarify the clinical characteristics and response to chemotherapy in patients with advanced LCNEC. From June 2002 to July 2004, nine patients (seven men and two women, median age 61) with advanced LCNEC were admitted to our hospital. We reviewed the clinical manifestations, tumor markers, and treatment of these patients. Seven of nine patients (78%) were current or ex-smokers. As for tumor markers, the levels of progastrin-releasing peptide (proGRP) and neuron-specific enolase (NSE) were elevated in six patients (67%) and five patients (56%), respectively. The diagnosis of LCNEC was made based on the resected specimens in 8 patients including resection of brain metastasis in 1 and CT-guided needle biopsy in 1. One patient was stage IIIA, 1 was stage IIIB, 3 were stage IV, and 4 had postoperative recurrence. Treatment included chemotherapy alone in 7 patients, chemotherapy plus whole brain radiation in 1, and postoperative radiotherapy in 1. Of 7 patients treated by chemotherapy alone who had received carboplatin-based chemotherapy. 5 showed partial response, yielding response rate of 71.4%. The proGRP level was frequently elevated in patients with advanced LCNEC and the response rate of LCNEC to carboplatin-based chemotherapy was comparable to that of small cell lung cancer.