A 79-year-old white woman who neither smoked nor chewed tobacco, developed oral florid papillomatosis with verrucous squamous carcinoma, associated with leukoplakia. These lesions repeatedly recurred following conventional treatment, viz, surgery, curettage, electrosurgery, and local application of tincture of podophylin. Oral florid papillomatosis should be regarded as premalignant eventuating in verrucous squamous carcinoma. A very favorable response to intermittent courses of oral methotrexate was evident.