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Although the therapeutic role of ajoene, an organosulfur compound of garlic, in cardiovascular diseases and mycology has been established, its usefulness in cancer treatment has only recently been suggested. We applied ajoene topically to the tumors of 21 patients with either nodular or superficial basal cell carcinoma (BCC). A reduction in tumor size was seen in 17 patients. Immunohistochemical assays for Bcl-2 expression in a selection of these tumors before and after treatment showed a significant decrease in this apoptosis-suppressing protein. On average, the percentage of tumor cells expressing the proliferation marker Ki-67 was not decreased, which suggests that the action of ajoene is not explained by a cytostatic effect. To obtain further insight into the mode of action of ajoene, the BCC cell line TE354T and a short-term primary culture of BCC were analyzed for apoptosis induction after treatment with the drug. Apoptosis was detected by morphology of the cells and by flow cytometry. Ajoene induced apoptosis in a dose- and time-dependent manner in these cultures. Taking together the results of the in vivo and in vitro studies, we conclude that ajoene can reduce BCC tumor size, mainly by inducing the mitochondria-dependent route of apoptosis.