We report a case of papillary squamous cell carcinoma of the lung developing in relation to a condylomatous papilloma and related to human papillomavirus (HPV) infection. The viral origin of the bronchial papillomatous lesion is strongly suggested by cytological and histological features with marked condylomatous changes. No viral capsid antigen was detected by immunohistochemistry. Transmission electron microscopy failed to reveal intranuclear viral-like particles in the papillary part of the carcinoma, but typical ultrastructural koilocytotic cells with irregular nucleus and coarse chromatin were observed. HPV DNA type 11 was detected by in situ hybridization using biotinylated probes on paraffin-embedded specimens, under stringent conditions (Tm-12 degrees, 50% formamide). Papillary squamous cell carcinoma may result from the malignant conversion of benign squamous papilloma of the bronchus. HPV type 11 may be associated with malignant conversion of benign papilloma of the pulmonary tract, as in the upper respiratory tract. In situ hybridization with biotinylated probes is a relatively simple and appropriate method for retrospective analysis of HPV DNA sequences in surgical specimens.