Seven hundred fifty-nine patients with Stage I/II breast cancer who were treated with mastectomy alone (558 patients) or breast-conserving surgery and tangential irradiation (201 patients) were evaluated. Median follow-up time was 34 months. Axillary node status showed differences between treatment groups. Seventy-two percent of patients undergoing lumpectomy and radiation therapy (Lx) versus 35% of patients in the mastectomy group were pathologically node-negative, 18% Lx versus 30% mastectomy alone had one to three nodes positive, and four or more positive axillary nodes were seen in 35% of mastectomy alone patients. Reflecting this trend, overall survival (P less than 0.007), time to locoregional failure (P less than 0.0005), and time to any failure (P less than 0.0001) favored Lx patients. Correcting for axillary node status, significant differences persisted only for node-negative patients. Median actuarial survival time was 73 months for the mastectomy alone group (196 patients) versus 120 months for the Lx group (144 patients) (P less than 0.02), with significant differences also noted in time to local failure (P less than 0.003) and time to any failure (P less than 0.001). Stratification according to primary tumor size in patients who were node-negative yielded marked differences in time to locoregional failure in T1 (less than 2 cm) (P less than 0.0006) presentations, with analysis approaching significance for T2 (2 to 5 cm) lesions (P less than 0.06). Disease-free interval was greater in node-negative Lx patients for both T1 (P less than 0.007) and T2 (P less than 0.05) presentations. Overall survival was not significantly different in node-negative Lx patients when primary tumor size was considered. Improved prognosis was identified in node-negative patients undergoing breast-conserving surgery and radiation therapy over mastectomy alone. Theoretical considerations included eradication of occult microscopic disease within the chest wall by tangential irradiation.