Overexpression of microRNA‐21 (miR‐21) has been observed in various cancer types, but little is known about the role of miR‐21 in melanoma. In this study, we demonstrate that levels of miR‐21 are significantly increased in primary melanoma tissues as compared to benign nevi and in human melanoma cell lines as compared to melanocytic cell preparations. We show that downregulation of miR‐21 in melanoma cell lines with high endogenous miR‐21 expression induced apoptosis, whereas proliferation was not significantly altered. Upregulation of miR‐21 in melanocytes resulted in increased proliferation and decreased apoptosis. However, in the MEWO melanoma cells with low endogenous miR‐21 expression, upregulation of miR‐21 had no functional effects. These findings indicate a potential pathogenetic role of miR‐21 upregulation in a subgroup of melanomas.