Irinotecan is a potent inhibitor of deoxyribonucleic acid topoisomerase 1 and the weekly schedule of 100-125 or 350 mg/m(2) administration on Day 1 every 3 weeks is recommended for recurrent small cell lung cancer. However, severe gastrointestinal toxic effects and myelosuppression are often observed in this dose setting. We conducted a retrospective study to evaluate the efficacy and safety of low-dose irinotecan monotherapy (60 mg/m(2) on Days 1, 8 and 15 every 4 weeks) as second-line chemotherapy for small cell lung cancer. The medical charts of small cell lung cancer patients who had received second-line chemotherapy at the National Cancer Center Hospital East between April 2003 and June 2012 were reviewed. Consecutive 57 patients who were treated with low dose of irinotecan (60 mg/m(2) on Days 1, 8 and 15 every 4 weeks) were analyzed in this study. Median age was 70 years (range, 51-83). Fifty-two (91%) were male, 36 (63%) had an Eastern Cooperative Oncology Group performance status 0-1 and 26 (46%) were sensitive relapse. The median number of chemotherapy cycles was 2. The objective response rate was 32% (95% confidence interval: 20-45%).The median progression-free survival and the median overall survival were 2.9 months (95% confidence interval: 1.9-3.4 months) and 5.3 months (95% confidence interval: 3.6-7.6 months), respectively. The incidence of Grade 3/4 neutropenia, diarrhea and nausea/vomiting was 21, 4 and 5%, respectively. Low-dose irinotecan monotherapy for recurrent small cell lung cancer might be effective with favorable toxicity. Randomized trial of 60 mg/m(2) versus standard dose of irinotecan is warranted.