Objective: To assess the significance of axillary lymph node status and tumor size for predicting locoregional recurrence (LRR) and overall survival after mastectomy for breast cancer and to discuss the utility of postmastectomy radiation therapy. Summary Background Data: Patients with locally advanced breast cancer require multimodality treatment combining chemotherapy (and/or hormonal therapy), surgery, and radiation. Randomized trials have demonstrated that postmastectomy radiation reduces LRR, but no overall survival benefit has been established. Methods: Criteria for accrual to the Alabama Breast Cancer Project (1975-1978) were female gender and T2-3 breast cancer with MO status. Patients underwent a radical or a modified radical mastectomy. Node-positive patients received adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy or adjuvant melphalan. Patients were evaluated for LRR and overall survival based on the number of positive axillary lymph nodes and (in NO patients) pathologic tumor size. Significance was determined using chi-square analysis. Survival curves were generated using the Kaplan-Meier method and were compared by log-rank analysis. Results: After median follow-up of 15 years, neither type of surgery nor chemotherapy was shown to affect locoregional disease-free or overall survival. LRR rates were higher and overall survival rates were lower in patients with nodal involvement, while tumor size was not shown to significantly affect these rates. Conclusions: Patients with axillary lymph node metastases may benefit from postmastectomy radiation, but the use of postmastectomy radiation in NO patients is not supported when it is based on tumor size alone.