The dysplastic nevus (DN) was first described by Clark in 1976. It was subsequently recognized to be a precursor of melanoma. Dysplastic nevi present with typical clinical and histological criteria. The dysplastic nevus syndrome (DNS) can be considered when at least two other family members have been shown to have multiple dysplastic nevi. From our own experience of over 2000 non-selected patients with melanoma only 60 (3%) were shown to have the DNS. In these 60 we could prove direct genetic penetration even though no HLA phenotype preference could be seen. Evaluation of the biological activity of the DN in cell cultures, as well as T-lymphocyte analysis in the neighborhood of the DN have shown signs of incipient malignant transformation of the DN. The practical implications of these findings and observations are discussed.