On the one hand, pretreatment tumor heterogeneity is mainly responsible for intrinsic drug resistance and relies on multiple mechanisms including the presence of cells in the tumor site expressing elements that bypass target inhibition because they promote aberrant downstream signaling (i.e., Ras oncoproteins in EGFR-hyperactivated tumors), or cells expressing MDR pumps, or cells endowed with potentiated DNA repair system, or cancer stem cell niches. The gene discussed is EGFR; the disease is neoplasm.