Aim. To determine whether topoisomerase II alpha (topolla) expression is an additional prognostic marker for less advanced stage laryngeal cancers first treated without surgery. Ki-67 and p53 protein levels were also assessed for comparison. Experimental design. Formalin-fixed, paraffin-embedded tumor material from 63 cases of squamous cell carcinoma (SCC) of the larynx (glottis, stages 0,1,2) was immunohistochemically stained for topolla, Ki-67 (MIB-1) and p53 (DO-7) and the results were compared with clinicopathologic findings. Results. There were 7 stage 0 (TisNOMO), 33 stage I (T1N0M0), and 23 stage II (T2N0M0) SCCs with the TNM classification. Significant differences between carcinomas and normal mucosa were found for the topoIIa-LI, Ki-67-LI, and topolla-to-Ki-67 ratio. Regarding histologic grade, a significant difference in topoIIa-to-Ki-67 ratio was evident between well or moderately and poorly differentiated lesions. There were 19 cases of recurrence and 44 cases of nonrecurrence, but no significant differences were found for either of the indices or their ratio. No significant variation with p53 positivity was evident with reference to histologic differentiation, T-factor, clinical course, or proliferation. Conclusions. The results demonstrate that the topoIIa-to-Ki-67 ratio is a more sensitive parameter reflecting proliferation, for histologic grading of less advanced laryngeal SCCs, than topolla- or Ki-67-LIs.