The morphology of the lesion and the site in which the lesion is found are the initial clues in classifying papillomavirus-induced neoplasia. Human papillomavirus (HPV) types have limited site-specificity and differ in their association with benign or malignant neoplastic development. Cytopathology, electron microscopy, antigen detection and molecular hybridization all play a role in the armamentarium of diagnostic methods. Although nitrocellulose blotting procedures provide the most accurate and sensitive method for detecting and characterizing viral nucleic acid sequences, recent improvements in cytological hybridization methods allow for rapid detection of virus and analysis of HPV type directly in biopsied tissue and in cervical smears. In particular, these in situ hybridization procedures facilitate retrospective studies of stored specimens.