Background: The most prevalent type of renal cell carcinoma (RCC) is clear cell RCC (ccRCC) representing 70% of RCC. Methyltransferase-like 3 (METTL3) is critical for carcinogenesis and cancer progression. Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) enhances collagen cross-linking and increases collagen stability. Epithelial Cadherin (E-cadherin) controls the actin cytoskeleton to preserve epithelial cell integrity.Aim: To demonstrate significance of METTL3, PLOD2 and E-cadherin IHC expression in ccRCC and their expressions were correlated with clinicopathological data & survival of the studied cases to find their potential prognostic role. Material and methods: This retrospective research was carried upon 50 cases of ccRCC immunohistochemically stained with METTL3, PLOD2 and E-Cadherin & the results were correlated with different clinicopathological variables and patients’ survival. Results: High METTL3 and positive E-cadherin were significantly related to younger patients’ age, small tumors < 7 cm, lower histologic grade, early tumor (T) stages, absence of regional lymph nodes and lower American Joint Committee on Cancer (AJCC) stage, better overall and progression-free survival (P