In October 2003, Jobs was diagnosed with cancer. In mid-2004, he announced to his employees that he had a cancerous tumor in his pancreas. The prognosis for pancreatic cancer is usually very poor; Jobs stated that he had a rare, much less aggressive type, known as islet cell neuroendocrine tumor.

Jobs resisted his doctors' recommendations for medical intervention for nine months, in favor of alternative medicine. According to Harvard researcher Ramzi Amri, this "led to an unnecessarily early death". Other doctors agree that Jobs's diet was insufficient to address his disease. However, cancer researcher and alternative medicine critic David Gorski wrote that "it's impossible to know whether and by how much he might have decreased his chances of surviving his cancer through his flirtation with woo. My best guess was that Jobs probably only modestly decreased his chances of survival, if that." Barrie R. Cassileth, the chief of Memorial Sloan Kettering Cancer Center's integrative medicine department, on the other hand, said, "Jobs's faith in alternative medicine likely cost him his life ... He had the only kind of pancreatic cancer that is treatable and curable ... He essentially committed suicide". According to biographer Walter Isaacson, "for nine months he refused to undergo surgery for his pancreatic cancer – a decision he later regretted as his health declined". "Instead, he tried a vegan diet, acupuncture, herbal remedies, and other treatments he found online, and even consulted a psychic. He was also influenced by a doctor who ran a clinic that advised juice fasts, bowel cleansings and other unproven approaches, before finally having surgery in July 2004." He underwent a pancreaticoduodenectomy (or "Whipple procedure") that appeared to remove the tumor successfully. Jobs did not receive chemotherapy or radiation therapy. During Jobs's absence, Tim Cook, head of worldwide sales and operations at Apple, ran the company.