Bone resorbing osteoclasts contain high amounts of tartrate-resistant acid phosphatase (TRACP) 5b and secrete it into the blood circulation. Circulating TRACP 5b activity is derived exclusively from osteoclasts. We have developed a TRACP 5b-specific-immunoassay using a monoclonal antibody O1A that was developed using TRACP 5b purified from human osteoclasts as antigen. Serum TRACP 5b activity has a low diurnal variability, and it does not accumulate in the circulation in renal or hepatic failure. It is elevated in 80% of patients with osteoporosis, while decreased 40-50% after antiresorptive therapy with estrogen and the bisphosphonate alendronate. Preliminary results show that serum TRACP 5b activity is normal in breast cancer patients without bone metastases, and elevated in approximately 80% of breast cancer patients with bone metastases. These results suggest that serum TRACP 5b activity may be a useful marker for the early detection of the spreading of breast cancer cells to bone.