Introduction: In the past, the prognosis of bladder cancer was dependent on the presence of muscle invasion. Recently High-Grade T1 (HGT1) Transitional Cell Carcinoma (TCC), found to be associated with similar behaviour and prognosis even following Bacillus Calmette Guerin (BCG) therapy. Recognition of new markers that may help in selection of high-risk cases that need aggressive treatment even in the early stage to avoid unwanted toxicity of chemotherapy has to be high priority. Aim: To evaluate the prognostic value of Octamer-Binding Transcription Factor 4 (OCT4) and Epidermal Growth Factor Receptor (EGFR) immunohistochemical expression in urothelial carcinoma of the bladder and their effect as well as the vascular invasion on the recurrence of these tumours. Materials and Methods: Prospective cohort study conducted in Zagazig University hospital from January 2010 till December 2013. Immunohistochemical staining of OCT4, EGFR and Cd34 for 68 cases of bladder cancer samples was done. The correlation between the expressions of each marker and clinic-pathologic parameters was then analyzed. Results: OCT4 was detected in 53 patients (77.9%) of total cases. EGFR showed high expression in 25 of cases. 18 and 25 cases revealed low and no EGFR expression, respectively. There was a significant association between intensity of OCT4 expression and tumour grade (p<0.001), muscle invasion (p<0.001), vascular invasion (p=0.004) and stage (p=0.001). Significant association was established between EGFR expression and tumor size, grade, lamina propria, muscle and vascular invasion and stage (p 0.005, <0.001, 0.001, <0.001, respectively). Significant association observed between OCT4, EGFR expression and vascular invasion and recurrence (p=0.026, 0.001 and 0.002 respectively). Conclusion: Using selective inhibitors for EGFR and OCT4 especially that approved for EGFR in treating selected cases of urothelial carcinoma of bladder could suppress tumor growth. These markers in addition to presence of vascular invasion have to be used in screening of high risk noninvasive group that benefits from target therapy.