A 50-year-old woman presented with local relapse of breast cancer 6 years after partial mastectomy. Relapse was accompanied by extended skin induration due to tumor cell embolization of dermal lymphatics. During the following years the patient was exposed to 11 different anti-tumor regimens including 13 cytotoxic drugs (including alkylating agents, antitumor antibiotics, vinca alcaloids, epipodophyllotoxins, and taxanes), 4 anti-hormonal, and 2 immunologic attempts. Paclitaxel achieved a prolonged local improvement for some 7 months, but further various treatments were ineffective. At that time gemcitabine therapy was initiated and tumor infiltration of the skin was visibly diminished only 2 weeks later. After that tumor regressed further for 5 months and remained stable with continued doses of gemcitabine during much of the woman's last year. The patient died of acute myeloid leukemia (AML) 4 years after the local recurrence of breast cancer. Since multiple treatments using a plethora of aggressive cytotoxic drugs may render several classes of chemotherapy agents ineffective due to cross-resistance, it seems advisable to select mild agents that are not subject to multidrug resistance mechanisms and display a unique mode of action as demonstrated in this case by gemcitabine.