Here, we report the construction and functional analysis of synthetic promoters designed for gene therapy applications requiring strong and specific gene expression in melanoma cell lines. We have analysed the transcriptional activity of different combinations of two transcriptional regulatory modules, a melanocyte-specific element from the human tyrosinase promoter and a cell-cycle-specific element from the human alpha-fetoprotein promoter. Transient expression assays in different cell lines show that several of these composite synthetic promoters can drive a strong and selective expression of a reporter gene in melanoma cell, providing us with a new powerful tool for gene therapy of melanomas.