Objectives: Urothelial carcinoma and prostatic adenocarcinoma are the most common tumors of genitourinary system. Both tumors can demonstrate a broad morphology or present as poorly differentiated carcinoma occurring in urinary bladder or prostate or both organs that raise the suspicion of a locally extending or metastatic carcinoma from either organs. Accurate distinction between these tumors is mandatory because of different tumor biology and therapeutic protocols. In equivocal tumor morphology, the primary option is to use immunohistochemical panel in surgical pathology that includes differentiation markers that will assist pathologists to avoid misdiagnosis. The aim of this study is immunohistochemical evaluation of GATA3 in urothelial carcinoma and prostatic adenocarcinoma with correlation to different clinicopathological parameters.Methods: We used formalin-fixed paraffin-embedded tissue blocks from 51 patients of urothelial carcinoma and 15 patients of prostatic adenocarcinoma including different grades, stages, and types. Monoclonal antibody for GATA3 was used for immunohistochemical staining of tissue sections, and GATA3 expression was semi-quantitatively scored using H-score method.Results: Of 51 urothelial carcinomas, 96% were GATA3 positive with a mean H-score = 212. No correlation between GATA3 expression and clinicopathological parameters includes grade and stage. Lower GATA3 expression was noted in urothelial carcinoma variants. All of prostatic adenocarcinoma cases did not show GATA3 reactivity.Conclusion: GATA3 reactivity is a reliable factor to confirm diagnosis of urothelial carcinoma and exclude prostatic adenocarcinoma. The routine use of GATA3 as differentiation marker for urothelial carcinoma may be advocated based on the results of this study.