Ten keratoacanthomas with both proliferative and regressive histologic features along with 10 well-differentiated squamous cell carcinomas were examined using immunohistochemistry for the expression of bcl-2, a protooncogene recently recognized to be involved in protecting cells from undergoing apoptosis. The squamous cell carcinomas had a modest but diffuse staining pattern, while the proliferative keratoacanthomas stained only at the basal cells and only rare cells stained positively in the regressive keratoacanthomas. The degree and pattern of staining suggest a loss of bcl-2 expression with tumor maturity in keratoacanthoma and a possible role in their ultimate involution.