A 74-year-old Japanese male patient with squamous cell carcinoma arising in an epidermal nevus is described. The patient had widespread warty lesions involving large parts of the body since infancy. Recently, a nodular lesion appeared on the middle part of his back and increased in size. Histologically, the nodule was diagnosed as squamous cell carcinoma and the warty lesion showed the features of epidermal nevus. The nodular lesion was totally excised and the skin defect was covered with split-thickness skin grafting. To the best of our knowledge, this is the 16th patient with malignant change of a verrucous epidermal nevus.