In this study, hyaluronan, laminin-1, tenascin-C and type VI collagen were measured in the sera of patients with stage I/II and stage IV melanoma. A significant increase in the serum levels of all four extracellular matrix proteins was found in patients with stage IV melanoma compared to healthy donors. Type VI collagen and hyaluronan serum levels were also significantly increased in stage I/II melanoma. Increased expression of the four matrix proteins was also demonstrated in melanoma cell lines using reverse transcriptase- polmerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). We suggest that tenascin-C, hyaluronan, laminin-1 and type VI collagen are involved in melanoma development and extracellular matrix remodelling during melanoma progression. This finding will be of interest in the development of serum markers for progression of malignant melanoma.