The harmful effects of tobacco use and nicotine are well known. There is strong epidemiological evidence for smoking as a risk factor for cancer of the lung and oral cavity. The evidence for second-hand smoke as a risk factor for breast cancer is rapidly accumulating. The anthracycline doxorubicin is used in the treatment of many types of malignancies, including breast cancer. The effect of nicotine on doxorubicin toxicity was evaluated in MCF-7 and KB-3.1 cancer cell cultures. Nicotine partially inhibited doxorubicin toxicity towards MCF-7 and KB-3.1 cells, as judged by clonogenicity and flow cytometry assays. Flow cytometric analysis showed that < 10% of cells treated with doxorubicin underwent apoptosis, while necrosis was the major mode of cell death. Inhibition of apoptosis and necrosis in cancer cells by nicotine can diminish the effectiveness of doxorubicin in cancer therapy.