This is the story of how one man's life's work allowed for Iodine-131 (I-131) to become a therapy for hyperthyroidism and thyroid cancer. What is now a standard in our times arose from Saul Hertz's rather challenging and humble beginnings. Thyroid lobectomy and total thyroidectomy were therapeutic mainstays for thyroid disease until Hertz treated his first patient with radioactive iodine (RAI) ablation therapy at Massachusetts General Hospital (MGH) on March 31, 1941. His concepts for using beta particle emission from RAI to ablate thyroid tissue were revolutionary. Hertz's RAI therapy translated to research with thyroid cancer by the mid-1940s. The high-energy beta particles produced cytolethal effects on remnant thyroid tissue left behind by total thyroidectomy, thereby accomplishing completion thyroidectomy in some patients. Progressive surgeons from the Hertz era incorporated RAI into their practice. MGH surgery resident Francis Moore took sabbatical from clinical training to do translational research with RAI and other radioisotopes. Irving Ariel of New York became known as a nuclear surgeon in the wake of Hertz's work. George Crile Jr of Cleveland became an RAI advocate for the surgical community, implementing several paradigm-changing concepts in thyroid disease along the way. Hertz was a visionary who sparked this movement, predicting many of the molecular dilemmas with RAI-tumor avidity that clinical researchers continue to navigate today. This timely history for surgical oncologists and endocrine surgeons traces the development of RAI therapy through the life of Saul Hertz, a biographical window influenced by social stigma, political controversy, and mainstream media.