The morphologic and immunophenotypical features of three embryonal and one spindle cell rhabdomyosarcomas that underwent marked cytologic differentiation after polychemotherapy are described. In all the cases the morphologic changes were associated to disappearance of vimentin immunoreactivity and intense positivity for desmin, muscle specific actins, and myoglobin; in addition the differentiated tumor cells acquired a strong and continuous pericellular staining for laminin. The mitotic activity was significantly decreased. Drug associated differentiation seems to recapitulate the normal myogenic development to the point that the more mature neoplastic cells may represent terminally differentiated elements withdrawn from cell cycle. However, due to the persistence of a small number of poorly differentiated rhabdomyoblasts, the clinical consequences of this phenomenon are unclear.