Soft tissue sarcomas, although sharing a mesenchymal origin, are a heterogeneous group of diseases. Nevertheless they are studied and frequently treated as if they were all the same. Recent developments suggest that a different approach may be more adequate. Genetic profiling studies have indicated that some soft tissue sarcoma subtypes, despite a distinct histo-pathological difference, may be closely related. Molecular biology research in addition has identified several subtype-specific oncogenes and their protein products that could serve as treatment targets. Since many of the new molecularly targeted agents do not induce tumour regression, but mainly result in growth inhibition, it is therefore necessary also to change the study end-point in screening studies in the search for active treatments. In view of all these it is proposed to consider using alternative end-points such as progression-free rates at pre-set times, or progression arrest at first evaluation. By using databases from large cooperative groups it should be possible to identify progression arrest rates for each specific subtype, and these could serve as reference for future trial design. Soft tissue sarcoma treatment and research will require a change of approach and necessitate global cooperation. (C) 2010 Elsevier Ltd. All rights reserved.