Dan Hammond, a father of six-year-old triplets, has been healthy when suddenly, he discovers a strange lump on his tailbone. He thinks surgery should've taken care of the problem, but later on, Dan deals with painful, swollen legs; insomnia; a sudden bout of vomiting; a bright pink spot on his neck; a skyrocketing fever; and vision problems, especially in his right eye. It turns out that Dan has an autoimmune disorder called polyarteritis nodosa. Since she was twelve years old, Lauren Warren has been suffering from a set of baffling symptoms. She has pain from her neck, down to her thighs; tachycardia; and reddish-colored urine that looks thick at the bottom. Surprisingly, Lauren's pain seems to disappear when she runs and consumes sports drinks and other sugary stuff. Then, she gets a tetanus shot after receiving a huge cut on her foot, and her attacks begin again with muscle twitches. After suffering for thirty years, Lauren learns that her body is producing too much heme from a genetic condition called porphyria.

Every year, millions of Americans fall prey to real-life medical mysteries ailments that go undiagnosed or misdiagnosed for years. Their lives are thrown into turmoil as medical professionals struggle to understand their baffling conditions. Mystery diagnosis tells their stories. Through interviews and dramatic recreations, each medical mystery is recounted in vivid detail. Symptoms emerge, specialists are called in, but still the daily struggle continues. And then one day, because of a patients relentless pursuit of an accurate diagnosis, or a forward thinking doctor, the problem is solved and a true diagnosis given.

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