Objectives:This study is aiming to assess the diagnostic value of p16 immunohistochemistry (IHC) for a variety of epithelial lesions in the service provided by the Department of Pathology at Sultan Qaboos University Hospital (SQUH), Sultanate of Oman. This study would enhance pathologists' ability to diagnose and differentiate between different types of epithelial lesions reliably. Methods:This study is a retrospective observational cross-sectional study. A total of 117 immunohistochemical tests for p16 were collected from the pathology lab at SQUH from January 2010 to December 2020. Data was analyzed using SPSS software. For numerical data, mean and percentages were used. For measuring the association between different pathological and clinical findings, the categorized variables were analyzed using the chi-square test. Results:Immunohistochemistry of p16 was mainly used to diagnose uterine cervical, ovarian, oropharyngeal and anal epithelial lesions. Predominately, it was applied on cervical intraepithelial neoplasia grades 1, 2 and 3 (CIN I, II, III), squamous metaplasia, chronic cervicitis, anal intraepithelial neoplasia as well as different types of squamous cell carcinoma, adenocarcinoma, and serous carcinoma. Conclusion:The results of the present study revealed the wide application of p16 IHC as a marker to reach the final histopathological diagnosis of epithelial lesions in the pathology lab at SQUH. The marker can be used effectively to differentiate between different types of lesions showing similar appearance on hematoxylin and eosin stain.