Epidermal growth factor receptor (EGFR) is an important target for tumor therapy in various tumors. The current understanding of EGFR conformations on the cell surface is based on X-ray structural data, molecular dynamic simulations, and fluorescence-localization imaging. Using scanning electron microscope (SEM) and transmission electron microscope (TEM) with the resolution at sub-nanometers, we successfully recognized individual molecules of EGFRs and their assembly details on the surface of triple-negative breast cancer (TNBC) upon one-to-one labeling by Au nanoparticles. Based on our results, we have proposed the possible configurations, structural models, and conformational transitions of EGFR oligomers. Our study shows that the high-resolution electron imaging is an invaluable tool to provide direct evidence of EGFR configuration on tumor cell surfaces, and may play a pivotal role in further understanding of EGFR-associated signaling and tumor therapy. (C) 2020 Elsevier Inc. All rights reserved.