Findings from 1665 women with primary breast cancer, treated at 34 NSABP institutions in Canada and the United States, have failed to demonstrate that patients with medial-central tumors had a greater probability of developing distant metastases or dying than did those with lateral tumors despite the greater incidence of internal mammary (IM) node involvement when tumors are medial-central in location. A comparison of patients with similar clinical nodal status and tumor location who were treated either by radical mastectomy (RM) or by total mastectomy plus radiation therapy (TM + RT) failed to indicate that radiation of IM nodes reduced the probability of distant treatment failure (TF) or mortality. When findings from patients having equivalent clinical nodal status and tumor location treated by TM alone or TM + RT were compared, it was found that the addition of RT failed to alter the probability of the occurrence of a distant TF or of death. This was despite the fact that in the nonradiated group two putative sources of further tumor spread, i.e., positive axillary and IM nodes, were left unremoved and untreated. The findings provide further insight into the biologic significance of the positive lymph node and confirm our prior contention that positive regional lymph nodes are indicators of a host-tumor relationship which permits the development of metastases and that they are not important investigators of distant disease.