Malignant melanoma is a devastating disease with a constantly increasing incidence worldwide and limited treatment options. MicroRNAs (miRNAs) are small non-coding RNA molecules which play a role in post-transcriptional gene regulation. It is becoming clear that aberrant expression of miRNAs has a role in cancerous transformation and progression. One of the largest miRNA clusters is on human chromosome 14q32. The aim of this study was to evaluate the involvement of miRNAs from the 14q32 cluster in the malignant progression of melanocytes to melanoma. This work shows that the majority of miRNAs mapped to chromosome 14q32 are significantly down-regulated or absent in melanoma cell lines, benign nevi and melanoma samples relative to normal melanocytes. This miRNA cluster has been shown to be down-regulated in different human malignancies. Three miRNAs from the Dlk1-Gtl2 cluster are part of major signaling pathways: the IGF1 signaling, the E2F cell cycle signaling and the NF¿B signaling, and involve in the tumor-genesis of melanoma.