We evaluated in vitro a series of telluride containing compounds bearing the benzenesulfonamide group, as effective inhibitors of the physiologically relevant human (h) expressed Carbonic Anhydrase (CA; EC 4.2.1.1) enzymes I, II, IV VII and IX. The potent effects of such compounds against the tumor-associated hCA IX being low nanomolar inhibitors (K<sub>I</sub> 2.2 to 2.9 nM) and with good selectivity over the ubiquitous hCA II, gave the possibility to evaluate their lethal effect in vitro against a breast cancer cell line (MDA-MB-231). Among the series, both compounds 3a and 3g induced significant toxic effects against tumor cells after 48 h incubation. Under normoxic condition 3a showed high efficacy killing over 94% of tumor cells at 1 µM, and derivative 3g reached the tumor cell viability under the 5% at 10 µM. In hypoxic condition, these two compounds showed less effective although retained excellent cancer cell killer. These unusual features make them interesting lead compounds acting as antitumor agents also in tumor types not dependent from hCA IX overexpression.