Genetic alterations in renal cell carcinoma (RCC) involve tumor suppressor genes such as Von Hippel-Lindau (VHL); proto-oncogenes such as MET and transcription factors such as TFE3 oncoprotein.To examine the clinicopathologic features and the expression of some oncogenic molecules in various RCCs in patients from Upper Egypt.The authors examined the expression pattern of pVHL; MET; and TFE3 proteins in 59 RCC using immunoperoxidase staining methods. The study group consisted of clear cell RCCs (CRCC); papillary RCCs type 1 (PRCC1); papillary RCCs type 2 (PRCC2); Xp11-2 translocation RCCs (XP11.2RCC); chromophobe RCCs (ChRCC); and sarcomatoid RCCs (SRCC).Variations were found in the expression of these molecules in the different types of RCCs. The mean age of RCCs among Egyptians was 52.70 ± 1.73 years; with male sex predominance. Mass lesion; pain; and hematuria were the main presenting features. Metastatic disease was more frequent with CRCC variant. pVHL expression was strong in PCRCC2; Xp11.2RCC; and ChRCC; moderate in CRCC; and weak in both PRCC1 and sarcomatoid RCC. MET protein expression was moderate in Xp11.2RCC; PRCC1; PRCC2; and sarcomatoid RCC. TFE3 protein expression was strong in Xp11.2RCC and PRCC2 variants. The expression was moderate in PRCC1; CRCC; ChRCC; and sarcomatoid RCC. Positive correlation was found in the expression of the different proteins (pVHL; MET; and TFE3) and some histological features (tumor grade; inflammation; necrosis and metastasis) and the presence of metastasis and some histological features (inflammation and/or necrosis).This study provides the first indication about the clinicopathologic features of RCCs in Upper Egypt. The variable expression of these molecules in the different variants of RCC suggests that several oncogenic pathways are operational in their development.