Serum levels of breast carcinoma antigen (CA 15.3) and urinary calcium excretion (UCa) were determined in 73 patients with breast cancer: 36 without bone metastases (stage I-IV) and 37 with bone metastases. The patients in the latter group were further investigated at 2,4 and 6 months from the start of treatment. Both markers showed significant elevations in the group with bone metastases (CA 15.3: P = 1.0×10–6, UCa: P = 8.6×10–9). The bone metastasis index (BMI), which represents the combination of the markers, had better diagnostic efficacy (90%) than CA 15.3 alone (84%) or UCa alone (82%). During treatment of bone metastasis, the longitudinal levels of the markers showed a highly significant association with the therapeutic response assessed by the UICC criteria. For identifying progression of disease, the diagnostic efficacy of CA 15.3, UCa and a combination of both, the so-called Biochemical Index of Response (BIR), was 65%, 70% and 79%, respectively, at two months and 89%, 84% and 92% at four months. Application of the tandem, CA 15.3 with UCa, was very useful for the detection of bone metastases and the prediction of response to therapy.