DNA topoisomerase II (Topo II) inhibitors are widely used in lung cancer chemotherapy, but small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) show different sensitivity to them. In this study, we examined the gene expression levels of both isoforms of Topo II (II alpha and II beta) in lung cancer specimens to investigate the differential expression between SCLC and NSCLC. The expression levels of the Topo II alpha and Topo II beta genes were assessed in 80 autopsy samples (40 primary tumors and 40 corresponding normal lung tissues) by using the reverse transcription polymerase chain reaction. We found that the expression levels of the Topo II alpha gene in tumors were significantly higher than those in normal lung tissues, and that those in SCLC were significantly higher than those in NSCLC. There were no significant differences in Topo II beta gene expression between tumors and normal lung tissues and between SCLC and NSCLC. Further-more, correlation analysis revealed that Topo II alpha expression was correlated with Topo II beta expression in both tumor and normal lung tissues. These results indicate that a difference exists in the regulation of the Topo II gene between lung tumors and normal lung tissues. Our finding of differential expression of Topo II alpha between SCLC and NSCLC also suggests that the Topo II alpha expression level is associated with sensitivity to Topo II inhibitors.