Background: Urothelial bladder carcinoma is a heterogenous disease with variable prognosis. The basal cytokeratin (CK5/6) is associated with basal molecular subtype of urothelial carcinoma and is speculated to be associated with aggressive tumor behavior. Aim: This study aimed to evaluate immunohistochemical expression of CK5/6, fibroblast activation protein (FAP) and CD147 in urothelial bladder carcinoma in relation to clinicopathological parameters, and to determine clinicopathological characteristics of CK5/6 positive urothelial carcinoma. Material and Methods: The current work included 60 cases of urothelial bladder carcinoma, which were subjected to immunohistochemical staining using CK5/6, FAP and CD147. The association between these markers' expression and clinicopathological parameters was assessed. Results: Positive expression for CK5/6 was detected in 48.3% of cases. CK5/6 immunoreactivity was significantly related to tumor grade (p-value = 0.002*), muscle invasion (p-value = 0.021*), squamous differentiation (p-value = 0.020*), FAP expression (p-value<0.001*), and CD147 expression (p-value=0.001*). No significant association was detected as regard patients' age, sex, or lymphovascular invasion. In turn, FAP expression in tumor microenvironment was significantly related to tumor grade and lymphovascular invasion, but not to muscle invasion or squamous differentiation. In addition, the expression of CD147 showed significant association with tumor grade and muscle invasion. Conclusions: Cytokeratin 5/6 expression in urothelial bladder carcinoma is associated with features of aggressive tumor behaviour (in terms of high tumor grade, advanced stage, and squamous differentiation), FAP and CD147 immunoreactivity. Such markers can be considered as progression markers for urothelial carcinoma.