Multidrug resistance (MDR) is the protection of a tumor cell population against numerous drugs differing in chemical structure and mechanisms of influence on the cells. Recent studies show that the molecular mechanisms of MDR are numerous. The most investigated mechanisms with known clinical significance are: a) alterations in the genes and proteins involved into the control of apoptosis ( especially p53, Bcl-2 and Bax); b) activation of transmemebrane proteins effluxing different chemical substances from the cells (P-glycoprotein is the most known efflux pump); c) activation of the enzymes of the glutathione detoxification system (like glutathione-S-transferase / (GST/); d) overexpression of the DNA mismatch repair enzymes (like MGMT); e) changing the expression level of target molecules (Topoisomerase II3). Hence this study tries to explore the role of p53, Fas, Bcl-2, Bax, P-glycoprotein, Topoisomerase II3, MGMT and GST/, in schistomal associated and nonschsitosomal associated transitional cell carcinoma (TCC) and squamous cell carcinoma (SCC) in correlation with different clinicopathological criteria which are tumor differentiation (grade) and muscle invasion by tumor (stage). Moreover, ex-vivo drug sensitivity testing using Differential Staining Cytotoxicity (DiSC) assay was used to investigate the impact of the expression status of different markers assessed on the sensitivity of tumor cells to different cytotoxic drugs namely, cisplatin, 5-flourouracil, vinblastine, mitomycin C and etoposide. A total of 70 cases of urothelial bladder cancer were included in this study. TCC was diagnosed in 48 specimens, while SCC was present in 22 cases. Schistosome eggs were identified in 14 TCC and in 14 SCC cases. The expressions of the previously mentioned genes were studied by immunohistochemistry (IHC), while Bax was studied by in situ hybridization technique. Moreover, single suspensions of tumor cells were prepared from fresh tumor specimens and used in DiSC assay In the current study, both of TCC and SCC cases showed a comparable positivity for p53, Pgp, MGMT and GST/ expression. Their positivity were about 35.4