A retrospective analysis was undertaken to assess the prognostic role of histologic findings in response to chemotherapy and survival in patients with metastatic breast cancer. Histologic material was available for 395 of 1587 patients treated for metastatic breast cancer at the M.D. Anderson Cancer Center between 1973 and 1984. Chemotherapy consisted of 5-fluorouracil, doxorubicin, and cyclophosphamide or similar drugs, with or without tamoxifen. Maintenance cyclophosphamide, methotrexate, and 5-fluorouracil was continued for 2 years after a cumulative doxorubicin dose of 450 mg/m2 was administered. The histologic distribution was as follows: infiltrating ductal carcinoma, 353; invasive lobular, 14; mixed histology, ten; mucinous, seven; signet ring, four; tubular, three; papillary, two; sarcomatoid, one; and apocrine, one. Because individual histologic types occurred infrequently, the patients were divided into infiltrating ductal and nonductal groups. Baseline patient characteristics included age, performance status, estrogen-receptor status, prior hormone response, disease extent, and levels of alkaline phosphatase, bilirubin, and lactate dehydrogenase. These were similar in the two groups. Significantly more patients with nonductal histology had greater than three metastatic sites. There were also more patients with hemoglobin less than 10 mg/dl and albumin less than 3.5 mg/dl in the nonductal group of patients. However, statistically these factors did not have an impact on the results. There was a 63% response rate (17% complete and 46% partial) for the ductal group and a 60% response rate (12% complete and 48% partial) for the nonductal group. The time from initiation of chemotherapy to disease progression was identical (12 months) for the two groups. Survival from initiation of chemotherapy was not significantly different (22 months for ductal and 27 months for nonductal). Based on this study, the authors conclude that histologic findings have no bearing on patient response to chemotherapy or survival in metastatic breast cancer.