The records of 35 patients with axillary metastases from a clinically occult primary treated at the U.T.M.D. Anderson Cancer Center between 1956 and 1987 were reviewed. The mean follow-up time is 121 mos for surviving patients (median 115 mos). Only patients with no clinical or mammographic evidence of a breast primary were included; those with a past history of breast malignancy or those whose metastases suggesting a non-breast primary on histologic review were excluded. Thirty-three of the 35 patients had mammography performed as part of their evaluation. Mean age was 51 yrs (32-72). The initial AJCC N stage was Nl in 25 patients, N2 in 7, one had supraclavicular adenopathy, and the clinical stage could not be determined in 2. Mastectomy was part of the initial therapy in 10 patients, and no primary tumors were found. Six of these 10 patients had post-operative radiation. An additional 6 patients had breast biopsy with positive results in 1. Twenty-five patients had their breast preserved: in 16 the breast was irradiated, in 9 it was observed. Seven of the 16 patients who had breast conservation with radiation therapy had N2 disease at presentation compared with l/9 of those who had their intact breast observed. Adjuvant chemotherapy was given in 14 patients, elective oophorectomy in one. The 5 and 10 yr actuarial survival rates are 68% and 64% for the whole group, with 49% freedom from relapse and 76% local control at both 5 and 10 yrs. The mean time to local relapse was 24 mos (8-47) in those who failed locally. Of the patients who did not have a mastectomy, 2/16 (12%) in the irradiated group, versus 5/9 (56%) in the qon-irradiated ~TFI~P had .sIrh,seq\lent manifestation of the primary in the breast; the primary \,,a~ then successfully treated in 5 of the 7 patients. Both of the patients who relapsed in the irradiated breast had had gross residual disease in the axilla prior to irradiation. One patient relapsed in the chest wall post-mastectomy, The axilla was irradiated in 12/23 patients who had an axillary dissection, and in 12 who had biopsy alone, 5 of whom had gross residual disease. The tumor recurred in the axilla in 1 patient who had axillary dissection and who had not had irradiation, and in none of the patients who had biopsy followed by axillary irradiation. Actuarial 5 yr survival is 86% for those who underwent axillary dissection compared with 42% of those who did not (p<.O5). The 5 yr survival is 73% for Nl disease with 82% local control, and 54% for N2 disease with 43% local control (P=NS). Arm edema occurred in 3 patients who had an axillary dissection plus irradiation. There was no significant difference in survival or local failure when those who had mastectomy or chemotherapy were compared to those who did not. The significant differences in local failure rates in those who had the intact breast irradiated compared to those who did not supports the recommendation for breast irradiation in patients who present with isolated axillary nodal metastases which are consistant with breast primary. Axillary dissection should be performed when feasible, and in cases of N2 disease, pre-operative systemic therapy would be expected to increase the likelihood of complete resection. All patients in this series would now be considered candidates for systemic therapy. The low local failure rate in those patients treated with breast conservation and irradiation, especially when the advanced nodal stage is considered, shows that breast conservation is feasible as a part of combined modality treatment.