Objectives: The present study was designed to investigate the efficacy of irinotecan monotherapy as a second-line treatment for small cell lung cancers (SCLCs). Methods: Irinotecan monotherapy was administered to 46 SCLC patients who were previously undergone cisplatin based chemotherapy protocols. Response to treatment, time to progression (TTP), overall survival rates and adverse events associated with irinotecan monotherapy (300mg/m2; total 153 cycles; mean 3.78 +/- 1.98) were determined, retrospectively. Results: Limited stage disease was diagnosed in 19.6% of patients (n=9) while 80.4% (n=37) were diagnosed with extensive stage cancer preceeding the irinotecan monotherapy. None of the patients had complete response to irinotecan. Partial response and stable disease were achieved among 17.5% of patients. Mean time to tumor progression (TTP) was determined to be 11.3 +/- 5.94 weeks while overall survival was 13.3 +/- 6.83 months. Considering adverse events, grade 3 and 4 toxicity was encountered in 8.9% and 4.5% of patients, respectively. Irinotecan monotherapy in brain metastasized tumors was found to be associated with significantly higher survival times compared with tumors lacking brain metastasis (15.0 +/- 5.95 vs 10.7 +/- 4.82 months; p<0.05). Conclusions: Irinotecan as a monotherapy in the second-line treatment of SCLC seems to have an acceptable level of toxicity and significant palliative effects. The prominent survival step-up effect particularly in brain metastasis patients appears worthy of note.