Since chemotherapy is not sufficiently effective, an alternative strategy for the treatment of advanced melanoma could be an in vivo gene therapy approach. For this purpose, a highly accurate delivery of the therapeutic gene and cell specific gene expression is essential. Since melanocytic cells are characterized by their pigmentation, and since tyrosinase is the key enzyme involved in melanogenesis, we studied the expression of a reporter gene which is under the control of the tyrosinase promoter or a combination of melanocyte-specific enhancer and tyrosinase promoter in ten human melanoma and four epithelial cell lines. Reporter gene expression was upregulated up to 21-fold using the tyrosinase promoter and up 154-fold using the enhancer/promoter construct compared to a control plasmid. Gene expression was strongly associated with capacity of cells for melanin synthesis. The results suggest that the use of tissue specific gene regulatory elements might provide a new opportunity for targeting therapeutic genes to melanoma cells.