Pulmonary pleomorphic carcinoma is a rare tumor of the lung, which is believed to spread at an early stage and to have an aggressive clinical course. The efficacy of chemotherapy for advanced pulmonary pleomorphic carcinoma has not been defined. The objective of this study was to evaluate the efficacy of palliative chemotherapy for pulmonary pleomorphic carcinoma. Thirteen consecutive patients who received palliative chemotherapy for advanced pulmonary pleomorphic carcinoma were investigated. All 13 patients were treated using chemotherapy regimens known to be active for the treatment of advanced non-small cell lung cancer (NSCLC). Eleven patients (85%) had progressive disease and two (15%) had stable disease after first-line chemotherapy. No patient achieved an objective response (objective response rate, 0%; 95% confidence interval, 0-23%). Of the 13, eight were given second-line chemotherapy, and all had progressive disease after second-line chemotherapy (objective response rate, 0%; 95% CI, 0-32%). Median overall survival from the initiation of first-line palliative chemotherapy was only 5 months (range, 2-12) with a median follow-up of 16 months. Advanced pulmonary pleomorphic carcinoma showed poor response to chemotherapy regimens that provide active treatment for NSCLC. Novel treatment approaches are required for pulmonary pleomorphic carcinoma.