The differential diagnosis between keratoacanthoma (KA) and well differentiated squamous cell carcinoma (WDSCC) is not always easy to perform. Seven cases of KA and seven cases of WDSCC have been here analyzed by morphometry on ultrastructural sections and compared with normal epidermis. Parameters expressing the cohesivity among epithelial cells (numerical and surface density of desmosomes; volume density of intercellular space) were significantly different in KA and WDSCC, so that they may be useful in differential diagnosis. The Authors also questioned the nature of KA, suggesting a continuum between this lesion and WDSCC.