Since musculoskeletal tumours comprise a large heterogeneous group of entities with different biological behaviour, clinical diagnosis of such lesions can be very difficult. The aim of this prospective study was to assess the usefulness of 2-[F-18]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in the non-invasive evaluation of soft tissue tumours. One hundred and two patients with suspected soft tissue neoplasms were investigated by FDG-PET. The uptake of FDG was evaluated semiquantitatively by determining the tumour to background ratio (TBR). All patients underwent biopsy, resulting in the histological detection of 39 high-grade sarcomas, 16 intermediate-grade sarcomas, 11 low-grade sarcomas, 25 benign tumours, 10 tumour-like lesions such as spontaneous myositis ossificans (n = 6) and one non-Hodgkin lymphoma. All lesions except for two lipomas disclosed an increased FDG uptake. Sarcomas showed significantly higher TBR values than latent or active benign lesions (P<0.001) and aggressive benign lesions (P<0.05). Using a TBR cut-off level of 3.0 for malignancy, sensitivity of FDG-PET was 97.0%, specificity 65.7% and accuracy 86. 3%. From our data there are three main conclusions: (1) Except for patients with pseudotumoral myositis ossificans, lesions with a TBR >3 were sarcomas (91.7%) or aggressive benign tumours (8.3%). (2) Tumours with a TBR <1.5 were latent or active benign lesions, exclusively. (3) The group with intermediate TBR values (<3 and >1. 5) comprised primarily latent or active benign lesions, but also four aggressive benign tumours and two low-grade sarcomas. Our data suggest that FDG-PET represents a useful tool for the evaluation of the biological activity of soft tissue neoplasms.