Rhabdomyosarcomas bear a morphological and genetic resemblance to developing skeletal muscle. Apart from myogenic marker genes (bHLH factors, myosin, actin), cell adhesion molecules such as N-cadherin and N-CAM have been reported to be expressed both in rhabdomyosarcomas and during myogenesis. The present study demonstrates the expression of another cadherin, cadherin-11, in rhabdomyosarcomas and during differentiation of myoblasts in vitro: cadherin-11, a predominantly mesenchymal cell adhesion molecule, is highly expressed in embryonal rhabdomyosarcomas and alveolar rhabdomyosarcomas, which do not bear the Pax-3-FKHR fusion previously described. Cadherin-11 is down-regulated in normal skeletal muscle and after myotube formation in vitro. The results of this study suggest that cadherin-11 might be involved in myogenesis and that rhabdomyosarcomas may re-express or fail to down-regulate cadherin-11. Since alveolar rhabdomyosarcomas bearing the t(2;13) translocation do not express cadherin-11, it is postulated that Pax-3 and cadherin-11 might be linked and involved in the same myogenic pathway.