Distinct differences between topical acid preparations can be detected by simple preclinical and clinical pharmacologic models designed to evaluate potential utility in the treatment of superficial skin tumors. The models distinguish a tissue-dissolving (ulcerating) effect from a tissue-fixation (mummifying) effect, as reflected by a distinct and lasting discoloration of hair in vitro or the skin surface in vivo. Double-blind clinical comparison of the response to different preparations of matched pairs of small superficial skin tumors in 33 subjects demonstrated for greater utility for nitric acid preparations of appropriate strength (6 to 7N), with added oxidizable organic acids, over the mineral acid alone. The nitrate reduction products generated in such preparations markedly speed up discoloration in the models and apparently contribute to the improved clinical utility of the topical treatment by enhancing the speed and intensity of tissue fixation, but not tissue erosion. The architecture of lesions eradicated by such mixtures is generally adequately preserved for histologic diagnosis of the extruded tissue.