Introduction: Bladder cancer is the most common malignancy involving the urinary system and the ninth most common malignancy worldwide. Ki-67 is a nonhistone cellular marker for proliferation. HER2/neu is an oncogene that plays an important role in the pathogenesis of many cancer types. In bladder carcinoma, its clinical significance remains under-investigated and poorly linked to the patients’ clinicopathological features especially with no reported Egyptian study. Aim: The aim of this work was to study the expression of HER2/neu and Ki-67 in urinary bladder carcinoma to evaluate their role in tumourigenesis and their correlation with other available clinicopathological variables associated with urothelial carcinoma. Materials and Methods: This cross-sectional study was conducted at the Department of Pathology, Faculty of Medicine, Cairo University, Egypt. Samples were paraffin blocks from 60 cases diagnosed with urothelial carcinoma underwent radical cystectomy. Ki-67 and HER2/neu immunohistochemical staining was done and of Ki-67 and HER2/neu Immunostaining was recorded. The associations between Ki-67, HER2/neu expressions and clinical and histopathological parameters of urothelial bladder carcinoma was evaluated. Results: The Ki-67 expression had significant association with tumour histological grade and lymphovascular invasion (p-value <0.05). The association of HER2/neu expression had significant association with perineural invasion (p-value <0.05). Conclusion: HER2/neu immunostaining was not associated with most of the clinicopathologic prognostic factors in urothelial bladder carcinoma.