Background: Extensive epidermal necrosis in newborn infants is an unusual event of heterogeneous cause. Objective: The objective of this article is to describe what seems to be a previously unrecognized lethal disease. Methods: The clinical and histopathologic features of three premature infants, two of them nonidentical twins, and the autopsy findings of one of them were analyzed. Results: Intrauterine lethal epidermal necrosis with hair follicle calcification, except for the face, hands, feet, elbows, and knees, was present in all three patients. Some histopathologic features were suggestive of epidermal apoptosis. Conclusion: We propose that the clinicopathologic alterations in our patients represent a new condition that may be caused by massive epidermal apoptosis.(J Am Acad Dermatol 1998;38:712-5.)