Dr. John Mendelsohn is credited for the concept of targeting the epidermal growth factor receptor (EGFR), providing the first evidence of anticancer activity of antagonist anti-EGFR mAb, and developing the Erbitux (Cetuximab) drug for cancer patients. During his professional journey, Dr. Mendelsohn also helped to build and elevate the status of three cancer cancers, all while touching the lives of cancer patients around the globe. He was a towering figure, and his passing in January 2019 casts a very long shadow over the entire field of cancer research and treatment. Although no one person can ever adequately fill John Mendelsohn's very large shoes, we can all learn by his remarkable example. Here we discuss Dr. Mendelsohn's professional life to spotlight his influence on oncology and also share personal reflections from us and several colleagues: Tony Hunter, Robert A. Weinberg, Robert C. Bast, Raymond Sawaya, David M. Gershenson, Christopher J Logothetis, Stanley R. Hamilton, Mien-Chie Hung, and George M. Stancel. See related article Kumar et al. Can Res 2019; 79:4315-4323.