Light microscopic studies have shown that nevus cell nests and melanoma nests are surrounded by basement membrane (BM) material containing type IV collagen and laminin. This study confirms this by electron microscopy and relates it to proteins which interact with the basement membrane. Nevi except for dysplastic and Spitz nevi, malignant melanomas, and melanoma metastases were studied by immunohistopathology, routine electron microscopy (EM), and immunoelectron microscopy. The lesions were incubated with monoclonal antibody (moAb) against type IV collagen, laminin, and the integrin α6 and studied by light microscopy. In addition, melanomas were studied by immuno-EM after incubation with a moAb against matrix metalloproteinase-2 (MMP-2). Nevus cell nests and melanoma nests are surrounded by BM material containing type IV collagen and laminin by immuno-EM. The BM material various in thickness and is amorphous. Type IV collagen, laminin, and MMP-2 are synthesized by melanoma cells as well as adjacent fibroblasts. Destruction or loss of the BM is not mandatory for melanoma invasion or even metastasis. Possibly the BM material is a protective wall for melanoma cells. Interactions between melanocytes and the extracellular matrix of which the BM is a part, can be traced back to the migration of melanocytes from the neural crest.