Muller et al. found that (i) within the same tumor, different cells express distinct EGFR or PDGFRA isoforms; (ii) multiple EGFR oncogenic variants are coexpressed in the same cell; and (iii) some cells express receptor and ligand other than EGFR or PDGFRA. These results suggest that heterogeneity of different tumor clones contributes to the failure of EGFR and PDGFRA inhibitors for glioma treatment. Here, EGFR is linked to central nervous system cancer.