Introduction: Urothelial carcinoma is the most common histologic type of urinary bladder cancer in Egypt. Detection of high-grade urothelial carcinoma is important for modification of therapy and improving the prognosis. P63 is expressed at high levels in the basal layers of different epithelial tissues, including the urothelium. Aim of the work: to study the diagnostic and prognostic value of p63 expression in urothelial carcinoma (UC).   Materials and Methods: Fifty cases of bladder urothelial carcinoma were involved in the study; 12 cases of non-invasive UC, (3 HG & 9 LG), and 38 cases of invasive UC, (30 HG & 8 LG). Sixteen cases of UC showed Bilharziasis. All the specimens were stained with p63 using immunohistochemical technique.  Results:  P63 was expressed in 28/38 cases (73.7%) of invasive UC and in all cases of non-invasive UC, and also in 16/17 (94%) low-Grade and in 24/33 (72.7%) of high-grade UC, with a statistically significant relation between p63 expression and both invasion (p > 0.001) and the tumor grade (p> 0.034). Conclusion: P63 can be used as a diagnostic and a prognostic factor for high grade invasive UC