The serum levels of osteocalcin, a 49-amino-acid bone-matrix protein, which is a biochemical parameter of bone formation, were measured in 61 patients with breast cancer. Breast cancer patients were subdivided as follows: (a) Patients in complete remission; (b) patients with visceral metastases (without bone metastases); (c) patients with bone metastases (with or without visceral metastases). Serum osteocalcin levels were significantly higher in patients with bone metastases than in patients in complete remission (P less than 0.005). When osteocalcin levels of patients with bone metastases were compared with those of an age-matched control group, serum osteocalcin levels were higher in the patients with bone metastases; however, the differences did not reach statistical significance. Serum osteocalcin levels of patients with visceral metastases (without bone metastases) were significantly lower than in control subjects (P less than 0.02). Our data demonstrate that serum osteocalcin levels are higher in breast cancer patients with bone metastases than in patients in remission. Bone formation, as reflected by serum osteocalcin levels, is decreased in breast cancer patients with visceral metastases.