Infection by the human papillomaviruses (HPV) represents an important risk factor in squamous lesions of various sites. More recently, data suggest that the glandular components of some tumors may also contain human papillomaviruses. This association may implicate HPVs in the genesis of these lesions as well. We present a longitudinal in situ hybridization study of HPV expression within a single patient, showing viral mRNA in squamous dysplasia, squamous and adenocarcinoma in situ, and in invasive adenosquamous carcinoma. There was continuity of the viral type (HPV 16) in the preinvasive and invasive portions of the lesions, and HPV mRNA was clearly demonstrable in the glandular components. The case illustrates the utility of in situ hybridization for the microscopic localization of viral gene expression, in addition to providing information about the viral type and perhaps the biologic potential of the lesion.