Objective: To describe the technique, applications and advantages of (18)FDG PET scanning in detection, analysis and management of musculoskeletal lesions. Design and patients: Forty-five patients (19 males, 26 females) aged 9 to 81 years had radiographs, routine radionuclide scans, CT and/or MRI of clinically suspected active benign or malignant musculoskeletal lesions. (18)FDG scans with a Siemens ECAT EXACT 921 dedicated PET unit (Knoxville, Tenn.) and FWH=6 mm. images acquired as a 5-6 bed examination (6 min emission and 4 min transmission) used OSEM iterative reconstruction with segmented transmission attenuation correction and a Gaussian filter (cutoff 6.7 mm). Region of interest (ROI) 3 x 3 pixel image analysis based on transverse whole body images (slice thickness 3.37 mm) generated Maximum Standard Uptake Values (Max SUV) with a cutoff of 2.0 used to distinguish benign and malignant lesions. Results: Thirty-nine studies were available for SUV ROI analysis. Overall sensitivity for differentiating malignant from benign osseous and non-osseous lesions was 91.7% (22/24), overall specificity was 100% (11/11) with an accuracy of 91.7%. All aggressive lesions had a Max SUV >2.0. Data separating benign from malignant lesions and aggressive from benign lesions were statistically significant (P<0.001) in both categories. There was no statistically significant difference in distinguishing aggressive from malignant lesions (P, ns). Conclusion: (18)FDG PET contributes unique information regarding metabolism of musculoskeletal lesions. By supplying a physiologic basis for more informed treatment and management, it influences prognosis and survival. Moreover, since residual, recurrent or metastatic tumors can be simultaneously documented on a single whole body scan, PET may theoretically prove to be cost-effective.