Extracellular matrix components can influence cell behaviour by modulating a wide variety of events. In particular, the glycosaminoglycan hyaluronan is involved in many processes of the normal and pathological adult cells and it is essential for embryonic development. Two main HA receptors have been characterized in vertebrate developing embryos: CD44 and RHAMM. These receptors display completely different characteristics apart from their ability to bind hyaluronan. RHAMM is still the most mysterious hyaluronan receptor as it can act as cell surface receptor but it can also be localized in the cytoplasm or in the cell nucleus, displaying both hyaluronan dependent and independent functions. In particular, the role of RHAMM during embryogenesis is still largely unclear. We reported a detailed gene expression analysis of RHAMM during Xenopus laevis development comparing its mRNA distribution with that of the hyaluronan synthases and CD44 genes, in order to provide a first insight into the possible role of RHAMM during vertebrate embryogenesis. Our findings point out that RHAMM mRNA displays a specific distribution in proliferating regions of the developing neural tube and retina where synthesis of hyaluronan is not detected. On the contrary, RHAMM expression correlates with the expression of hyaluronan synthase-1 and hyaluronan-receptor CD44 gene expression in migrating cranial neural crest. These results suggest that during the central nervous system development RHAMM could be involved in cell proliferation and migration processes both in a hyaluronan independent and dependent manner.