The diagnosis and differential diagnosis of malignant soft tissue tumors not infrequently poses great difficulties, especially in those cases which lack any feature of differentiation by conventional light microscopy. These difficulties have been partially resolved through the application of ultrastructural investigations. Recently considerable progress has been achieved using immunohistochemistry. At the Kiel Pediatric Tumor Registry we were able to reduce the percentage of unclassified soft tissue sarcomas from 17.6% in 1982 to 4.5% in 1989. Particularly useful were antibodies against the different types of intermediate filaments, muscle-specific actin, myoglobin, and the neural markers neuron-specific enolase and protein S-100. In contrast to the expected immunophenotype rhabdomyosarcomas, malignant peripheral neuroectodermal tumors and malignant schwannomas showed expression of cytokeratins. Moreover, in many cases rhabdomyosarcomas and synovial sarcomas expressed neural markers. Ewing's sarcoma and malignant peripheral neuroectodermal tumor are histogenetically related, but differ in grade of neural differentiation. In all soft tissue sarcomas immunohistochemistry is very useful to obtain information on the cellular heterogeneity. Despite the great achievements not every soft tissue sarcoma can be diagnosed with certainty. There will always be a baseline of unclassified cases due to problems which are not caused by the tumor itself but rather by diagnostic circumstances.