Using a sensitive and specific radioimmunoassay we have developed for the determination of human calcitonin (HCT) in unconcentrated peripheral blood, we propose to study the levels of this hormone in patients with cancer of the breast. Calcitonin is a hypocalcemic, hypophosphatemic polypeptide hormone secreted by the C cells of mammalian thyroid. In 1973 we reported finding increased levels in 35% of cancer patients with spontaneous hypercalcemia. During a study of normocalcemic patients with bronchogenic cancer, it became apparent that over 55% of these patients had calcitonin levels above normal. Was this hypercalcitonemia in response to bone resorption and impending hypercalcemia? Could calcitonin be used as a marker in cancer? Coombes et al. confirmed the high incidence of hypercalcitonemia in bronchogenic cancer and, in addition, showed that 100% of the patients they studied with breast cancer with skeletal metastases had high values of blood calcitonin which could be augmented by calcium infusion. In our laboratory a preliminary study of 44 patients showed that patients with distant metastases who were not on therapy had higher calcitonin levels than those with disease confined to the breast. Only one patient with apparently localized disease had an elevated calcitonin value. During the proposed study, we will evaluate the possible usefulness of serum calcitonin as a parameter for the extent of metastases, prognosis, and response to therapy.