Bladder carcinoma is an endemic problem in Egypt with schistosomiasis being an additional risk factor. Due to gender disparities, Er beta investigation and its role in modulating chemosensitivity are studied. CD117/KIT expression is also considered since the emergence of the targets of the tyrosine kinase inhibitor imatinib mesylate (Gleevec). HER2 is one of the established therapeutic targets in many cancers. We aimed to investigate CD117/KIT immunoexpression in schistosomal and non-schistosomal urothelial carcinoma of Egyptian patients and its relationship with HER2 and Er beta expressions, correlating it with pertinent variables that will help to provide better treatment options of possible combined targeted and hormonal therapy that might be effective against this aggressive malignancy. Sixty cases of bladder carcinoma were tested. Depending on the schistosomiasis association status of each case, two groups have been established with 30 cases each. CD117/KIT, HER2, and ER beta immunostaining were done and correlated with clinico- immuno-pathological parameters. CD117/KIT expression was seen in 71.7% of cases that correlated significantly with schistosomiasis (P = 0.01). In addition, a positive correlation was detected between schistosomiasis association and the percentage of immunostained cells and intensity score of CD117/KIT with P = 0.027, 0.01, respectively. 30% and 61.7% of cases were positively stained with HER2 and Er beta, respectively, with no significant relation with schistosomiasis. Due to the high expression, we found further clinical trials are needed to offer individualized targeted therapeutic options in urothelial tumors using anti-CD117/KIT, HER2, and ER beta other than limited traditional chemo- and nontargeted therapies.