There are diseases that puzzle doctors. Patients with these diseases often remain undiagnosed for years and some will die without an accurate diagnosis. The diagnosis of patients with mysterious diseases, many of which are rare diseases, can entail a long, complex, and detailed process that requires specialist knowledge and investigations. Patients and families often have a sense of relief upon receiving a diagnosis. A diagnosis can reduce uncertainty and fear and is essential to ensure appropriate medical treatment (if available), support, and health-care coverage.