BACKGROUND: Basal cell carcinoma (BCC) is one of the most frequent forms of malignancy in humans. Although BCC is a tumour of low degree of malignancy, if left untreated, it can be locally aggressive, eat away at tissues and cause ulceration. Nodular is the most common subtype of BCC (>50%). Although apparently non-invasive, micronodular, a certain subgroup of nodular, is likely to recur. Glycosaminoglycans (GAGs), such as hyaluronic acid (HA), are extracellular matrix molecules of high importance in malignant transformation, metastasis and other complex remodelling processes.OBJECTIVES: To investigate the expression of GAGs and their metabolizing enzymes in nodular BCC, when compared with adjacent healthy human skin tissue specimens.METHODS: Total GAGs were isolated and purified from nodular BCC and normal adjacent human skin tissue specimens. GAGs were subsequently fractionated by electrophoresis on cellulose acetate membranes and characterized using specific GAG-degrading enzymes. The content of HA in total GAGs was measured using ELISA and the expression of HA synthases (HAS), hyaluronidases (HYAL) and HA receptors (CD44 and receptor hyaluronic acid-mediated motility (RHAMM) was assessed using RT-PCR.RESULTS: Nodular BCC is associated with increased levels of HA concomitant with upregulation of gene expression of HAS3, HYAL3 and RHAMM, when compared with normal adjacent skin.CONCLUSION: These results indicate that HA homeostasis in nodular BCC shows distinct features which may be helpful in understanding the complex behaviour of nodular subtype of BCC, thus eventually leading to new treatment strategies.