We investigated the localization of type XV collagen in normal human skin and skin tumors by immunohistochemical methods using a monoclonal antibody against the recombinant polypeptide of the non-collagenous region of the alpha1 chain of murine type XV collagen. Type XV collagen was localized in the dermo-epidermal, perivascular, and perineural basement membrane zones in normal skin. While this localization appeared to be similar to that of type IV collagen, detailed observation revealed that its localization was distinct in fact from that of type IV collagen which was thin and linear in appearance and was distributed inside organs. Type XV collagen was distributed broadly and zonally outside organs such as vascular and neural tissues. It was expressed at low levels in seborrheic keratosis and not expressed at all in actinic keratosis and squamous cell carcinoma. Melanocytic nevi and malignant melanomas in situ were positive for type XV collagen; melanomas with dermal invasion were negative. These findings suggest that type XV collagen plays a role in the adherence of the basement membrane to surrounding connective tissue and that it may be associated with the tumorigenesis of keratinocytes and melanocytes.