It is often difficult to assess accurately the nature of a skeletal lesion. Problems include differentiating a malignant from a benign bone tumor, as well as determining the cause of a pathologic fracture. Such fractures may occur through osteoporotic bone as well as through neoplasm-affected bone. Thus, development of an imaging modality capable of distinguishing between such lesions is of importance. During 1996, we ran a prospective study in which results of Tc-99m-methyl-diphosphate (MDP) bone scans were compared with those of sestamibi (MIBI) bone scans and with subsequent biopsy and clinical course. The results of the bone scans were assessed by 2 independent "blinded" observers, and the ratios of counts in lesions to those in normal tissue (L/N ratios) were calculated. In cases of malignant (7) and benign (8) tumors, intensity of uptake in MDP scans were not predictive of degree of aggressiveness. On the other hand, MIBI bone scans demonstrated significant difference in intensity of uptake between benign and malignant bone tumors (L/N ratios 2.05 vs 2.75). In 5 of 8 benign lesions the L/N ratio was 1. In the others, increased uptake was minimal. In 2 patients changes in uptake in MIBI bone scan following chemotherapy appeared to be related to the degree of tumor necrosis achieved. While the MIBI bone scan cannot replace tissue biopsy as a definitive diagnostic modality in bone neoplasms, it does appear to allow better preoperative assessment and prognosis.