We hypothesize that during RCC progression in cellular microenvironment the growth factors imbalance, in consequence of higher expression levels of mitogenic growth factors and lower levels of antiproliferative growth factors, such as high EGF or TGFα, and low levels of TGFβ1, could create a hiper-activation of the oncogenic EGF-TGFα/EGFR pathway, enhancing cancer progression and the acquisition of metastatic phenotypes. The gene discussed is EGFR; the disease is renal cell carcinoma.