Unlike light and electron microscopy of cross sections of tissue, scanning electron microscopy (SEM) combined with immunological labeling is useful in localizing molecules expressed on the cell surface. The topological distribution of molecules of intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1) and human leukocyte antigen-DR (HLA-DR) on the epidermal-dermal interface is reviewed in normal and pathological specimens of human skin. Our method for preparing such an interface for SEM study entails separating the epidermis from the dermal connective tissue and immuno-gold labeling. Mycosis fungoides is one condition in which the lymphocytes infiltrate the epidermis without damaging the keratinocytes, while the lichenoid reaction constitutes a contrasting model in which the cells remain beneath the epidermis, damaging the keratinocytes. Based on the differential distribution of these molecules expressed on the epidermal-dermal interface, we proposed a new concept of “epidermal clearance” of neoplastic cells in accordance with the continuous desquamation.