Ezrin, podocalyxin and paxillin are cytoskeleton-associated proteins, implicated in several malignancies, but their role in Urothelial carcinoma of the bladder (UCB) is still controversy. We investigated the expression of those markersin UCB and the association of their expression pattern with clinicopathological parameters.Quantitative rt-PCR analyses used to examine mRNA level of ezrin and paxillinin23 fresh specimens of UCB and adjacent normal mucosal tissues from patients undergoing cystoscopy.Also, immunohistochemical evaluation of ezrin, podocalyxin and paxillin was performed on 123 paraffin blocks of UCB. Ezrin mRNA levelwas significantly high in normal mucosa than in UCB (p=0.012) while paxillinmRNA level wasn'tsignificant (p=0.34). Significant negative correlation was found between membranous ezrin immunoexpression and prognostic parameters as grade,T-stage and recurrence(p=0.001, p<0.0001and p= 0.002 respectively). Regarding paxillin immunoexpression,significant negative correlation was detected with grade andT-stage (p<0.0001). Membranous expression of podocalyxin was significantly correlated with grade, T-stage and recurrence (p=0.016, p= 0.003 and p<0.0001respectively). A significant correlation was found between three markers.These results suggest that ezrin, podocalyxin and paxillin could be valuable prognostic molecules in evaluation of UCB and this might lead to establishment ofnew molecular therapeutic strategy and prognostic biomarkers in UCB.