The aggressiveness of laryngeal squamous cell carcinoma (SCC) is unpredictable. Topoisomerase (Topo) II-alpha is an essential nuclear enzyme; its expression rises at the end of the S-G2/M phase and drops at completion of mitosis. This study sought to determine if Topo II-alpha expression can serve as a prognostic factor in laryngeal SCC. Specimens from 56 consecutive patients were immunohistochemically stained for Topo II-alpha, and the number of positive cells in the areas of highest staining was counted in 3 highpower fields (X400) (Topo II-alpha index). Differences in the Topo II-alpha index by the presence or absence of recurrence, tumor stage and grade, and disease course were analyzed statistically. On multivariate Cox regression analysis, the Topo II-alpha index (>70 or < or =70) (P = .008) and tumor grade (P = .034) independently predicted disease-free survival. These findings suggest that high Topo II-alpha expression may be a useful indicator of tumor aggressiveness and poor outcome in laryngeal SCC.