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The diagnostic term atypical squamous cells of undetermined significance (ASCUS) was introduced with the Bethesda System to describe cervical/vaginal smears displaying cytologic changes of uncertain clinical significance. The diagnosis does not identify a specific entity, but reflects one of the inherent limitations of the pap screening procedure. Cervical/vaginal cytology cannot always distinguish reactive from dysplastic changes. Specific cytomorphologic criteria, guidelines for the management of ASCUS diagnoses, the risk of underlying dysplasia, and the natural history of ASCUS have been published. Recently, stratification of ASCUS cases by morphologic features and testing for human papillomavirus have been studied. However, the diagnosis itself remains poorly understood and controversial. The controversy is caused in part by the lack of consistency and reproducibility of ASCUS diagnoses, but it also is related to the struggle to define a modern approach for screening and managing preneoplastic lesions of the uterine cervix.