p53 immunohistochemistry has been used for decades in the evaluation of solid organ malignancies. It is widely employed in gynecologic pathology in the assessment of predominantly endometrial but also ovarian carcinomas. Both these tumor types exhibit a dual pathway model of carcinogenesis, with p53 loss or overexpression commonly seen in more aggressive cancers. p53 immunostaining has now evolved into a surrogate marker for the TP53 mutation status of these carcinomas. Urothelial carcinoma shares a dual pathway model of carcinogenesis with these gynecologic malignancies such that FGFR3 mutations are over-represented in the low-grade urothelial pathway with TP53 mutations seen in the high-grade urothelial pathway. Intuitively, it would seem that p53 immunoexpression should follow a similar pattern in urothelial carcinoma. Historically, p53 expression in urothelial carcinoma has been assessed using a variety of cut-offs, most commonly a 10% level of tumor nuclear expression. However, this assessment does not consider the “null” expression pattern which is known to associate with TP53 mutations.