Background: Growing interest have been recently directed towards roles of cancer metabolism in carcinogenesis with “Warburg effect" being the signature of cancer metabolism. Pyruvate kinase M2 (PKM2) is a crucial regulator of the Warburg effect. Epidermal growth factor receptor (EGFR) has been also involved in different metabolic pathways. Aim: This study aimed to investigate the immunohistochemical expression of PKM2 and EGFR in urothelial carcinoma. Furthermore, we analyzed the relation between PKM2 and EGFR with the available clinicopathologic parameters. Materials and Methods: PKM2 and EGFR immunostaining was performed on 70 specimens of urothelial carcinoma of the urinary bladder. Results: PKM2 was highly expressed in 62.9% of cases. High PKM2 expression was significantly associated with high-grade (P=0.003), muscle invasion (P=0.002), advanced T staging (P=0.001) and concomitant carcinoma in situ (P=0.013). EGFR expression was detected in 68.6% of cases. EGFR expression was significantly higher in high-grade tumors (P=0.013), muscle-invasive tumors (P