A particularly aggressive form of oral leukoplakia that commences with a hyperkeratosis, spreads to become multifocal and verruciform in appearance, and later becomes malignant has been termed proliferative verrucous leukoplakia. Ten patients with persistent multifocal verruciform white patches were investigated. Lesions were often bilateral and affected predominantly mandibular alveolar and buccal mucosa. At first biopsy no lesion was graded higher than a verrucous hyperplasia, but subsequently all patients had squamous cell carcinoma, and two patients have died of their disease. Lesions were managed with surgery, carbon dioxide laser, and photodynamic therapy. The patients presented here confirm the existence of proliferative verrucous leukoplakia as a clinicopathologic entity. Careful examination of the whole mouth is essential when a hyperplastic white patch is seen to check for possible proliferative verrucous leukoplakia. Early aggressive treatment must then be started, and regular long-term review is crucial.