Uterine carcinosarcomas (UCs) are highly aggressive neoplasms for which no effective adjuvant therapy has been established. The aim of this study was to test potential indicators of UC sensitivity to topoisomerase I (topo I)-targeted drugs. Laboratory studies have shown that the cellular response to topo I-targeted drugs is dependent on topo I expression, DNA replication rate, and activity of the apoptotic pathway. Therefore, this study investigated expression of topo I, a proliferation marker Ki-67, and the apoptosis initiator p53 in 20 cases of UC. Formalin-fixed paraffin-embedded tissue sections were immunostained with monoclonal antibodies against topo I, Ki-67, and p53. The hospital records of all 20 patients with UC were reviewed. Twelve (60%) of 20 cases showed increased expression of topo I. Staining for Ki-67 showed elevated expression in 15 (75%) of 20 cases. Fourteen cases (70%) showed positive staining for p53 in more than 20% of the tumor cells. However, analysis of the relationship between immunohistochemical results and clinical parameters revealed no correlations with topo I expression. There were no significant correlations between the expression of topo I and Ki-67 (P = .704), or topo I and p53 (P = .465). Significantly increased expression of topo I, Ki-67, and p53 in UC tumor cells suggests sensitivity to topo I-targeted drug treatment.