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Cytologic-histologic correlation (CHC) represents a documented effort to obtain and compare, when available, gynecologic cytology reports with an interpretation of high-grade squamous intraepithelial lesion or malignancy, with the subsequent histopathology report, and to determine the possible cause of any discrepancy. The correlation is influenced by multiple closely interdependent clinical and pathologic factors. Many of these factors including the sensitivity and accuracy of colposcopy-directed biopsy, the diligence of the colposcopist, and the attributes of the cervical lesion represent “preanalytical” factors which can significantly affect the CHC outcome, but are often less emphasized during CHC process. The status of “gold standard” of cervical biopsy histology will be less “golden” if clinicians miss, during colposcopy, the lesion which had been flagged by cytology. CHC also serves as one of the important assurance tools to monitor and improve the pathology laboratory overall quality, and the ability of the pathologists to enhance their diagnostic interpretation. As pathologists, we should make every effort to improve on CHC, by applying systematic approaches, both in technical laboratory and interpretive diagnosis, which increase yield and reduce diagnostic discrepancies. The widespread use of Human Papilloma Virus testing and p16 immunohistochemistry have significantly enhanced diagnostic accuracy both in cytology and in histology. Herein, we review the intimate relationships and factors that may govern discrepancies between cytology, colposcopy-directed biopsies, and biopsies with subsequent Loop Electroexcision Procedure for cervical squamous intraepithelial lesions. Ultimately the projected risk for high-grade squamous intraepithelial lesion and cancer and the suggested management guidelines are directly tied in with effective CHC.