Hailey-Hailey disease is a recurrent, autosomal dominant vesiculobullous dermatotis with a predilection for intertrigenous areas. We report what we believe to be the first case of squamous cell carcinoma arising de novo in a skin lesion of Hailey-Hailey disease. The occurrence of malignant neoplasms arising in the skin lesions of Hailey-Hailey disease and other acantholytic dermatoses is reviewed.