Nasal inverted papilloma is usually a benign tumor but is associated with squamous cell carcinoma in about 10% of cases. To determine the etiological role of human papillomavirus (HPV) in inverted papilloma and to clarify the relationship between the different types of human papillomavirus and malignant transformation, we analyzed retrospectively a series of 29 formalin - fixed, paraffin-embedded cases, 3 of which had squamous cell carcinoma. A highly sensitive and specific modification of the polymerase chain reaction (PCR) was used to detect the E6 gene sequences of HPV 6/11, 16 and 18. HPV was present in 20 of the cases (69%), HPV 6/11 in 14 (48%), HPV 16 in 19 (65%) and both HPV 6/11 and 16 in 13 of the specimens (45%). HPV 18 was not identified in any specimen. In all three of the squamous cell carcinomas based on inverted papillomas, HPV 6/11 and 16 were detected. These results were in agreement with other studies. While HPV is related etiologically to inverted papilloma, we suggest that HPV 16 may be involved in its malignant transformation.