We investigated the utility of the erythrocyte sedimentation rate in planning the diagnostic and surgical strategy for patients who were found by conventional radiography to have a solitary skeletal lesion. A series of 101 patients was separated into two groups according to their ultimate diagnoses. Group I included patients with skeletal metastases of unknown origin, unusual bone infections, and marrow cell tumors. Group II included benign and malignant primary bone tumors. Using the Westergren method to determine the erythrocyte sedimentation rate prior to biopsy, we found that only one of 65 Group II patients had a rate above 30 mm/h whereas 22 of 36 Group I patients had rates greater than 60 mm/h. By using Receiver Operating Characteristic analysis, we estimated the trade-offs between sensitivity and specificity that can be achieved with various threshold sedimentation rates. In particular, we found that a critical erythrocyte sedimentation rate of 30 mm/h allows separation of Group II patients from Group I patients with 96.9% sensitivity and 82.6% specificity. Our results indicate that the erythrocyte sedimentation rate can be used effectively in conjunction with conventional radiography in the planning of an appropriate further diagnostic strategy.