Verrucous carcinoma of the larynx is a distinct and uncommon variant of well-differentiated squamous cell carcinoma. By DNA hybridization techniques, we clearly demonstrated human papillomavirus (HPV-16-related) sequences in five patients with this neoplasm. In addition, HPV-16-related sequences were found in adjacent normal tissues. The DNAs from squamous cell carcinomas of the larynx were negative when hybridized to HPV-6, -11, or -16. Postirradiation anaplastic transformation of verrucous carcinoma has been described. We believe that radiotherapy should not be given unless the potential consequences are fully explained because of its potential to activate or alter HPV-16-related sequences.