Fluorine-18 labelled alpha-methyltyrosine (FMT) was developed for positron emission tomography (PET) imaging, and its potential for clinical application in patients with brain tumours has been demonstrated. This is the first trial to compare FMT with 18F-fluoro-2-deoxy-D-glucose (FDG) for the evaluation of musculoskeletal tumours. Seventy-five patients were examined with both FMT- and FDG-PET within a 2-week period. Imaging findings were visually inspected in conjunction with computed tomography and/or magnetic resonance imaging, and standardized uptake values (SUVs) for both FMT and FDG in lesions were also generated and compared with histological findings. A significant correlation between FMT and FDG SUVs was found for all lesions (r=0.769, P<0.0001), and mean values for malignant tumours were significantly higher than those for benign lesions in both FMT- and FDG-PET. The diagnostic sensitivities and specificities for malignancy were 72.7% and 84.9%, respectively, using FMT with a cut-off SUV of 1.2, and 72.7% and 66.0%, respectively, using FDG with a cut-off SUV of 1.9. The resultant accuracy with FMT was 81.3%, higher than that for FDG (68.0%), and the difference with respect to specificity was significant (chi2cal=5.0625, P<0.05). On the other hand, while a significant correlation was found between malignant tumour grade and SUV with both FMT- (rho=0.656) and FDG-PET (rho=0.815), only the latter demonstrated significant differences among grades I, II and III. FMT and FDG for PET appear equally effective at detecting musculoskeletal tumours. In evaluating musculoskeletal tumours, FMT may be superior to FDG in the differentiation between benign and malignant tumours, while FDG may be the better choice for non-invasive malignancy grading.