For public and professional acceptance, clinical studies in breast cancer must be scientifically necessary and ethically justifiable. To resolve controversy based upon retrospective data, they must be prospective and randomized. These guidelines have been used by the National Surgical Adjuvant Breast Project in its investigations carried out during the past 15 years in numerous cooperating institutions. Neither thio-tepa adjuvant to radical mastectomy, nor prophylactic oophorectomy, nor post-operative radiation therapy were found to prolong life. Therefore, prophylactic oophorectomy is contraindicated and adjuvant chemotherapy cannot be justified except perhaps under special circumstances and as part of carefully controlled clinical trials. Postoperative radiation therapy, even in the presence of positive axillary lymph nodes, cannot be recommended except to minimize the rate of local skin recurrences.The present study addresses itself to the timely controversy surrounding proper management of axillary lymph nodes in primary breast cancer. Does removing them alter the outcome of therapy? Total (simple) mastectomy is being compared with radical mastectomy. Women with clinically negative nodes on physical examination are treated either by total (simple) mastectomy alone or by total mastectomy plus radiation, or by radical mastectomy. When the nodes are clinically positive, either radical mastectomy or total mastectomy followed by radiation is being used.The protocol, now underway more than a year, has been well accepted by patients and by many well informed physicians and surgeons. In years ahead it will provide objective evidence as to whether or not removal of the axillary lymph nodes alters the therapeutic efficacy of mastectomy in the treatment of primary breast cancer.