Pulmonary pleomorphic carcinoma is an uncommon malignant tumor of the lung, which has the dual cell components of spindle or giant cells and epithelial cells. The objective of this study was to investigate the clinical course and efficacy of palliative chemotherapy in patients with advanced pulmonary pleomorphic carcinoma. Twelve patients were diagnosed with advanced pulmonary pleomorphic carcinoma and received palliative chemotherapy from February 2000 to December 2007. Among the 12 patients, five patients received gemcitabine/cisplatin, three patients received gemcitabine/carboplatin, two patients received paclitaxel/carboplatin, one patient received paclitaxel/cisplatin, and one patient received docetaxel/cisplatin as first-line chemotherapy. The median patient's age was 62 (range, 32-72 years). Among the 12 patients, nine patients had relapsed disease after curative resection and three patients had metastatic disease at the initial presentation. After treatment with first-line palliative chemotherapy, seven patients (58%) had progressive disease, three patients (25%) had stable disease, and only two patients (17%) had a partial response. The median overall survival from the day of initiation of first-line chemotherapy was only 8 months (95% CI, 6-10) with median follow-up of 26 months. These results showed the dismal prognosis and the poor response to chemotherapy of advanced pulmonary pleomorphic carcinoma. Further studies are needed to investigate whether the current strategy of palliative chemotherapy for the treatment of advanced pulmonary pleomorphic carcinoma can be justified or not. Moreover, additional novel treatment approaches are required.