Numerous tumor markers such as CEA, MCA, CA 15-3 have been assayed in breast cancer patients to detect relapse at a preclinical stage and most of all to monitor the treatment of the advanced disease. Since they are not site-specific, pyridinium crosslink dosage has recently been reported as a specific bone resorption marker in several non neoplastic diseases. The aim of this study was to evaluate the urinary pyridinium crosslink levels in breast cancer with or without osseous involvement, and to correlate it with serial doses of CA 15-3. 285 breast cancer patients (226 free of disease and 59 with bone metastases) were measured for both pyridinoline and CA 15-3. In the metastatic patients the mean values of the two markers were significantly higher than in non evident disease patients (P = < 0.01 and p = < 0.001 respectively). Abnormal values over the normal were found in 22% for pyridinoline and 11% for CA 15-3 in patients free of disease while the normal values observed in patients with bone metastases were 22% for pyridinoline and 39% for CA 15-3. Tandem dosage of CA 15-3, was highly sensitive but site-aspecific, and pyridinoline, which is bone specific, may be useful chiefly in the monitoring of breast cancer treatment, since many physiological conditions such as age, menopausal status and variation over 24 hours, and cost effectiveness will influence the use of pyridinoline during follow-up.