Varmus was born to Beatrice, a social Service worker, and Frank Varmus, a physician, Jewish parents of Eastern European descent, in Oceanside, New York. In 1957, he graduated from Freeport High School in Freeport, NY and enrolled at Amherst College, intending to follow in his father's footsteps as a medical Doctor, but eventually graduating with a B.A. in English literature. He went on to earn a graduate degree in English at Harvard University in 1962 before changing his mind once again and applying to medical schools. He was twice rejected from Harvard Medical School. That same year, he entered the Columbia University College of Physicians and Surgeons and later worked at a missionary hospital in Bareilly, India, and the Columbia-Presbyterian Hospital. As an alternative to serving militarily in the Vietnam War, Varmus joined the Public Health Service at the National Institutes of Health in 1968. Working under Ira Pastan, he researched the regulation of bacterial gene expression by cyclic AMP. In 1970, he began postdoctoral research in Bishop's lab at University of California, San Francisco.