A retrospective analysis of 859 patients who developed bone metastases from breast cancer between 1975 and 1991 was performed in order to identify factors that predict for complications from skeletal disease. The patients were divided into four groups based on the sites of disease at diagnosis of skeletal metastases: bone disease only; bone and soft tissue disease; bone and pleuro-pulmonary disease; bone and liver disease. Patients with metastatic disease confined to the skeleton were most likely to develop a pathological fracture. The time to long bone fracture was similar for all groups, but the least number of such fractures occurred in patients with bone and liver metastases since their survival was shortest (median: 5.5 months; P<0.001). Patients with bone metastases only were most likely to require radiotherapy to painful osseous deposits (P=0.0001) and most rapidly developed spinal cord compression (P=0.01, data not shown). The results suggest that patients with disease confined to the skeleton at the diagnosis of bone metastases are most likely to develop skeletal-related complications from advanced breast cancer. Such patients may benefit most from treatment with bisphosphonates.