Background: p16 is a tumor suppressor protein important in regulating cell cycle. In bladder cancer, p16 mutations are widespread and tend to be more prevalent in low-grade superficial tumors than in higher-grade invasive tumors. Objective: To evaluate expression of p16 in 25 cases of cervical squamous cell carcinoma and 25 cases of urinary bladder squamous cell carcinoma. Patients and methods: This study was carried out in the Histopathology Department of Al-Azhar University Hospitals and from some private laboratories during the period from August 2019 up to January 2020. H & E stained sections were prepared from paraffin blocks for revision of diagnosis. Immunohistochemical analysis was done on 4 micron sections of formalin-fixed paraffin-embedded tissue using the labeled streptavidin-biotin method after antigen retrieval. Antibodies against P16 were utilized on sections from paraffin blocks. CINtec Histology kit includes a two-step antibody method for detection of human p16 antibody. Results: Expression of P16 was positive in 92% of cases of squamous cell carcinoma of the uterine cervix and 60% of cases squamous cell carcinoma of the urinary bladder. In patients with cervical squamous cell carcinoma, there was statistically significant relation between intensity of P16 staining and tumor grading. In patients with squamous cell carcinoma of the urinary bladder, there was a statistically significant relation between intensity of P16 staining and tumor grading and staging. Moderate/strong staining intensity can predict staging 2B among patients with squamous cell carcinoma of the uterine cervix, and negative/weak staining intensity can predict staging 1A, 1B, 2A with sensitivity 52.9% and specificity 37.5% among patients with squamous cell carcinoma of the urinary bladder. Conclusion: p16 immunohistochemical expression alone should not be used as a marker for differentiation between cervical and urinary squamous cell carcinoma.