The designation CD44 describes a group of type I transmembrane proteins which share N-terminal and C-terminal sequences. These molecules differ in the central extracellular domain by the use of sequences encoded by ten variant exons which may be completely absent or included in various combinations and by cell type specific addition of glycosaminoglycan and carbohydrate moieties. Expression of variant proteins is observed in normal tissues such as on keratinocytes, dendritic cells and activated lymphocytes in the adult organism and on morphogenetically active epithelium such as the apical ectodermal ridge (AER) in the embryo. Certain CD44 proteins expressed on the AER can act as low affinity fibroblast growth factor receptors and are vital for epithelial-mesenchymal cell communication. CD44 variant proteins have also been implicated in tumour growth and metastasis and we speculate that CD44 mediated growth factor presentation may also be decisive in metastasis formation. Molecular strategies designed to block growth factor presentation by CD44 may aid in the therapy of metastatic cancer.