Background: According to results of National Population-based Cancer Registry Program, bladder cancer became the second after liver cancer among Egyptian males. About 70% of bladder cancers are diagnosed as non-muscle invasive cancers with high risk of recurrence beside the risk of progressing to muscularis propria invasion. The challenge is to identify non –invasive cancers with reliable method for accurate diagnosis as well as predicting the prognosis. Aim: We aimed to evaluate immunohistochemical expression of Claudin-1and Claudin-4 in invasive and noninvasive urothelial lesions and correlate them with clinico-pathological findings. Methods: This retrospective study included 36 different cases of urinary bladder lesions designated as; 30 cases of urothelial carcinomas and 6 papillary urothelial neoplasms of low malignant potential (PUNLMP) in addition to 6 normal control cases. Cases were graded according to WHO classification and staged according to TNM pathological staging system. Slides were subjected to Immunohistochemical staining by claudin-1 and claudin-4. Results: Claudin-1 had the highest level of expression among carcinoma cases, while claudin -4 expression showed the highest expression among control cases (p˂0.000 for both). Increased claudin-1 expression was significantly related to muscle invasion(P=0.000) (r=0.668), advanced T stage(P=0.000) (r=0.697) and high tumor grade(P=0.012) (r=0.452). Claudin -4 expression showed significant statistical difference as regards urothelial carcinomas without muscle invasion (P=0.000) (r= -0.732), earlier T stage and low tumor grade(P=0.006) (r= -0.494). Conclusion: Claudin -1&4 could be used as potential markers to differentiate invasive from non -invasive and LG from HG urothelial carcinoma. They can predict the clinical outcome and take part in assessment of patients with UC.