Background: Conservation of the breast is one of the major goals of modern breast cancer surgery. Despite several advances in surgical technique and adjuvant multimodahty treatment, very large tumors or those with unfavorable localization remained subject to mastectomy until recently. We wanted to find out if preoperative chemotherapy has an impact on the reduction of tumor size and if subsequently breast-conserving surgery could be offered to these patients. Patients and Methods: We report on 48 patients suffering from biopsy-proven breast cancer, who would have been treated with mastectomy when conventional criteria would have been applied. In an individualized multimodahty treatment approach, these patients were treated using preopertive cytotoxic chemotherapy. Study end points are the clinical and pathological response rates and the surgical method which could be applied at the end of their preoperative treatment. Results: Overall, in 41 out of 48 patients (85%), we observed at least partial response to the treatment, 6 (13%) patients had a complete pathological response at the time of their operation. 33 patients (69%) received a breast-conserving surgical procedure, and only 15 (31%) had to undergo mastectomy. Conclusions: Preoperative chemotherapy is an extremely valuable tool in the treatment of large breast cancers. Reduction of tumor size took place in almost all of the patients and led to breast conservation in a substantial number of patients who would have underwent mastectomy without this treatment. There are several questions regarding preoperative chemotherapy currently under debate, e.g., the optimal duration of treatment or the best agents. In particular, the question whether these initial responses had a favorable impact on long-term results can only be clarified by prospective trials, which are currently under way in many breast cancer centers.