Our main objective was to revisit RCC drug transport activity in vitro by employing specific fluorescent substrates, and characterize the impact of methylation and EGFR inhibition on the expression of the characteristic renal drug transporters, namely organic cation transporters 1 and 2 (OCT1 and OCT2), P-glycoprotein (P-gp), and the breast cancer resistance protein (BCRP). Here, ABCG2 is linked to renal cell carcinoma.