Between 1974 and 1986, 283 patients with ten or more positive nodes were treated in four prospective trials using doxorubicin-containing adjuvant chemotherapy. At a median follow-up of 92 months, 182 patients had had a recurrence, and 158 died. An estimated 41% and 37% were disease-free at 5 and 7 years, respectively. Patients with ten positive nodes had a significantly better disease-free survival than those with more than ten such nodes (P = 0.04). The disease-free survival rate and overall survival rate were not influenced by the estrogen receptor status of the tumor, patient age, or disease stage. Long-term data on a large number of patients treated at this institute showed the natural history of this subgroup of patients. Approximately 30% of patient survived disease-free at 10 years after treatment with the systemic therapies used in these protocols. Newer approaches are needed to alter the prognosis of this subgroup of patients further.