['Tumor-based biomarkers of outcome for patients with clear cell renal cell carcinoma (ccRCC) remain limited, especially for those with low-risk disease. Type IIa topoisomerase (TOPOIIa) is a well-known biomarker of DNA replication and a target for antineoplastic agents, but it has not been evaluated as a biomarker of ccRCC outcome.', 'To evaluate the association of TOPOIIa expression in ccRCC and risk of cancer-specific death following surgery.', 'Two independent cohort studies were studied in tertiary referral urology practices in the United States. We identified cohorts of 1378 (analytic) and 279 (validation) patients who underwent nephrectomy for clinically localized ccRCC and had paraffin tumor tissue available. TOPOIIa expression was assessed using immunohistochemistry and scored as the number of positive cells per square millimeter.', 'Our primary end point was cancer-specific survival (CSS). We evaluated TOPOIIa expression as a continuous variable and dichotomized as low versus high. For associations with CSS, we used Kaplan-Meier curves and Cox regression models.'] Is higher expression of topoisomerase II alpha an independent marker of increased risk of cancer-specific death in patients with clear cell renal cell carcinoma?