Ten biochemical parameters, each of which has been individually advocated in the past as a tumor-index substance for breast cancer, were measured in 5 1 patients with breast disease, 42 of whom had active breast cancer. All patients with overt metastatic breast cancer had abnormalities of at least three of these parameters, of which ferritin (88%), carcinoembryonic antigen (81%) and Creactive protein (81%) were most commonly abnormal. Many combinations of two markers will detect all of these patients and the incidence of biochemical abnormalities in this group compared favorably with the results of physical methods of detecting metastases. Eleven (73%) out of 15 patients with disease apparently localized to the breast and draining lymph nodes, but who were considered to have a poor prognosis (Grade 3 tumor; T4 tumor; involved axillary lymph nodes) had at least one abnormal biochemical parameter. Three of these 11 patients have subsequently developed overt metastases within a year of mastectomy. However, these abnormalities were spread over a wide range of parameters and measurement of a total of seven index substances would be needed to detect all these patients. These preliminary data, however, tend to indicate that patieqts in this group, with both histology indicating a poor prognosis and an abnormal biochemical profile, will relapse sooner than the other patients, and that such a group may benefit from systemic therapy in addition to local treatment of their breast carcinomas.