The aim of this study was to assess the value of 99mTc-hexakis2-methoxyisobutylisonitrile (MIBI) scintigraphy in patients with clinical and radiologic features of primary or metastatic musculoskeletal tumors.The scintigraphic findings for 84 patients were compared with the surgical and histologic findings. Each patient underwent three-phase bone scanning with 99mTc-methylene diphosphonate (MDP) and dynamic and static MIBI scintigraphy. The MIBI scans were evaluated by visual and quantitative analysis. The count ratio of the lesion to the adjacent or contralateral normal area (L/N) was calculated from the region of interest drawn on the MIBI scan. The Mann-Whitney test was used to determine the differences between the uptake ratios of malignant and benign lesions.Although increased MDP uptake was not specific for bone malignancy, a significant difference was found between benign tumors (L/N = 1.22 +/- 0.43) and malignant tumors (L/N = 2.25 +/- 1.03) on MIBI scans. Sensitivity and specificity were 81% and 87%, respectively. Forty-six of 53 proven benign lesions did not show significant MIBI uptake. The negative predictive value was 88%. In all seven sites of pathologic fracture, significant uptake was seen. However, three malignant lesions were not detected by MIBI scintigraphy, whereas seven benign lesions showed false-positive results.The major diagnostic worth of MIBI scintigraphy is its high negative predictive value. Although not capable of replacing tissue biopsy as a definitive diagnostic modality for musculoskeletal neoplasms, MIBI scintigraphy does appear to have a role in better preoperative assessment and in distinguishing between pathologic and simple fractures.