Tenascin is an extracellular matrix glycoprotein that is widely expressed during embryogenesis. In adults, it is restricted to select sites, including certain epithelial-stromal interfaces, but is notably enhanced in active inflammatory-reactive processes and in the stroma of many neoplasms. The authors immunostained with the monoclonal antibody (MAb) 100EB2 cryosections of vulvar and cervical biopsies displaying convincing koilocytosis with variable degrees of hyperplasia-dysplasia; in situ carcinomas were included. The presence of human papillomaviruses (HPV) 6, 11, 16, 18, 31, or 33 was confirmed by in situ hybridization in a subset of cases. Findings were compared with normal controls. The study was extended with the MAb 143DB7 that reacted with tenascin in paraffin sections. In normal samples, tenascin immunoreaction appeared as a delicate, continuous rim, in the immediate vicinity of the laminin staining; in parakeratotic areas, the rim was thicker. In foci of hyperplastic-dysplastic epithelium with or without koilocytosis, a distinct increase in tenascin staining was noted; enhanced tenascin often paralleled increasing hyperplasia and dysplasia. In most cervical and vulvar carcinomas in situ, the reactions were intense and extended deeply and raggedly into the underlying stroma. Tenascin was selectively enhanced in the endocervical stroma around inflammed or metaplastic glands. The authors conclude that tenascin is increased in HPV infection associated with epithelial proliferation. Enhancement was most consistently strong and extensive in in situ carcinomas, suggesting a correlation with active phases of epithelial growth and stromal remodeling.