The current paper presents Chapter 5 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening, which deals with the histopathological diagnosis of lesions of the uterine cervix. It completes a series of publications in journals containing the contents of other parts of the European Guidelines. Histopathology provides the final diagnosis on the basis of which treatment is planned, and serves as the gold standard for quality control of cytology and colposcopy. It is also the source of the diagnostic data stored at the cancer registry and used for evaluation of screening programmes. It is therefore important that histopathology standards are monitored and based on agreed diagnostic criteria. Histology is required to diagnose the degree of abnormality in women with persistent low-grade abnormalities including HPV-lesions, as well as high-grade lesions. Cytology may also suggest either glandular abnormalities or be suggestive of high-grade CIN, AIS or invasive cancer. Histopathologists should be aware of, and familiar with, the nature of cytological changes which may be relevant to their reports. The accuracy of the histopathological diagnosis of tissue specimens depends on adequate samples, obtained by colposcopically directed punch biopsies (with endocervical curettage if necessary) or excision of the transformation zone or conisation. An accurate histological diagnosis further depends on appropriate macroscopic description, technical processing, microscopic interpretation and quality management correlating cytological and histological diagnosis. This paper proposes guidelines for sampling and processing of cervical tissue specimens obtained by biopsy, excision and/or curettage.