Background: Bladder cancer is globally the ninth, most common malignancy, and the thirteenth most common cause, of cancer death, associated with high morbidity and mortality, if not treated optimally. Bladder cancers can be divided into molecular subtypes, referred to luminal and basal with distinct clinical behaviors. HER2 is one of the established therapeutic targets in many cancers. Claudins are tight junction proteins, known to modulate therapy resistance in cancer cells. Aim: This study aimed to assess Claudins and HER2 status in the context of tumor molecular subtypes, identified by GATA3 and CK5/6 expression, that may help to select urothelial carcinoma patients, most likely to respond to immunotherapy. Materials and Methods: This retrospective study was done upon 50 cases of conventional urothelial carcinoma. GATA3, CK5/6, HER2, Claudins1&4 and P53immunostaining were done and correlated with clinico-immuno-pathological parameters. Results: Bladder cancers could be assigned to main intrinsic molecular subtypes, referred to luminal, basal and double negative. Basal & double negative bladder cancers were more aggressive, when compared to luminal cancers. Positive significant statistical correlation was found between HER2, claudin1 and P53 and clinic-immuno-pathological parameters as tumor size, grade, TNM stage, LVI, tumor budding and aggressive molecular subtypes (P-value< 0.05). Negative significant statistical correlation was found between claudin4 and fore mentioned clinico-immuno-pathological parameters (P-value< 0.05). Conclusions: The molecular subtypes of bladder cancers, HER2, claudin1&4 and P53 can be used for prognostic and therapeutic stratification of bladder cancers patients, and may affect patient outcome.