Cyclooxygenase-2 (COX-2) is an enzyme that plays an important role in the production of prostaglandins. Numerous studies have demonstrated increased levels of COX-2 in human cancers of different types. It is thought that COX-2 may be involved in the development and progression of malignant tumours. However, data on the changes in COX-2 expression during the development and progression of human melanoma are relatively limited. Moreover, the results reported by different groups disagree to a large extent. The aim of this work was to evaluate whether COX-2 protein might be considered a potential molecular marker of melanoma progression. The expression of COX-2 was determined immunohistochemically in formalin-fixed, paraffin-embedded specimens of 64 human melanocytic skin tumours (17 naevi, 36 primary cutaneous melanomas and 11 lymph node melanoma metastases, with six pairs of primary and metastatic lesions obtained from the same patients). It was found that the expression level of COX-2 was dependent on both the stage and histopathological type of the melanoma. Collectively, our data indicate that changes in the expression level of COX-2 are correlated with the development and progression of human melanoma, and imply that the COX-2 protein may be considered a potential prognostic and predictive marker in malignant melanoma.