Aim of the study. - Etoposide, a Topoisomerase II inhibitor agent, is currently being explored as a therapeutic agent for brain tumors. The aim of this experimental study was to compare the in vitro etoposide sensitivity of human glioma cells vs human squamous cell carcinoma (SCC) cells. Material and methods. - Twelve human cell lines (six malignant glioma cell lines and six head and neck SCC cell lines) were used for this comparative study. A standard colony formation assay was used to assess cell survival. Since Topoisomerase II is the critical target for etoposide, it was of interest to determine Topoisomerase II activity and etoposide induced inhibition of Topoisomerase II activity for the glioma cells vs the SCC cells. Results. - Except for etoposide-induced inhibition of Topoisomerase II activity, no difference was found for etoposide sensitivity and Topoisomerase II activity between the both type of cells. Conclusion. These results suggested that the Topoisomerase II reactive agents may prove to be clinically a useful drug for patients presenting with malignant gliomas.