Since musculoskeletal tumours comprise a large heterogenous 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-3-deoxy-D-glucose (FDG) positron emission tomography (PET) in the non-invasive evaluation of soft tissue rumours. One hundred and two patients with suspected soft tissue neoplasms were investigated by FDC-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 rumours, 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%) os aggressive benign rumours (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.