Small cell lung cancer is characterized by an aggressive clinical course and a high tendency for early dissemination in spite of a good chemotherapy response. Topotecan is a topoisomerase I inhibitor, and it is used as second-line treatment for small cell lung cancer. The reported dose-limiting adverse reactions to topotecan are mainly hematologic. Yet pulmonary toxicity associated with topotecan is known to be rare. We report here on a case that showed the development of acute respiratory distress syndrome during the 3rd cycle of topotecan chemotherapy in a patient with small cell lung cancer. He developed dyspnea and respiratory failure, and the chest CT scan revealed diffuse ground-glass opacity that was probably due to chemotherapy-related pulmonary toxicity. He finally died of acute respiratory distress syndrome.