High-risk human papillomavirus (HPV) initiates a series of precancerous changes in the cervical squamous epithelium. If untreated, these may lead to the development of cervical carcinoma. The virally induced changes are reflected in histomorphological and immunophenotypic alterations that predict the biological behavior of the precancerous lesions. Recent years have seen clarification and more consistent application of terms used to describe these alterations and increasing convergence of diagnostic approach, culminating in the most recent terminology recommended by the Lower Anogenital Tract Squamous Terminology Standardization (LAST) project for HPV-associated lesions. This chapter covers the evolution of the current terminology, the epidemiology, and molecular biology of HPV and cervical squamous preneoplasia and the current approach to histopathological diagnosis of these lesions.