Transepithelial elimination of elastic fibers is frequently seen in keratoacanthoma. However, the mechanism underlying this elastic fiber transport is not yet fully understood. We investigated the process by comparing the related features of 27 cases of keratoacanthoma, eight cases of squamous cell carcinoma and 11 cases of seborrheic keratosis (control). Microscopically, transepithelial elimination of elastic fibers was specifically observed in keratoacanthomas. Elastic fibers were surrounded by keratoacanthoma cell membrane and were ultrastructurally associated with hemidesmosomes and the basement membrane. Collagen fibrils were also observed within small, membrane-delineated vesicles within cells in the lower layers of the tumor. Also noted was strong expression of matrix metalloproteinase-1, which was detected by immunohistochemical analysis and in situ hybridization. Western blotting showed significantly stronger labeling of matrix metalloproteinase-1 in samples of keratoacanthoma than in normal epidermis. In contrast, squamous cell carcinomas and seborrheic keratosis exhibited none of the aforementioned characteristics. We propose that keratoacanthoma cells entrap, lift and eliminate elastic fibers as they proliferate and keratinize toward the epidermal surface, while simultaneously phagocytosing collagen fibrils. In that regard, matrix metalloproteinase-1 appears to play a key role in the degradation of collagen fibrils.