This chapter presents a state of the art summary of Mahvash disease relation to its biology, epidemiology, disease mechanisms, clinical signs, diagnosis, treatment and prognosis. Mahvash disease was initially noted in 2007 in a 60-year-old female patient who presented with abdominal pain, mild hypoglycemia and elevated glucagon levels without symptoms of glucagonoma syndrome. The inactivating glucagon receptor mutations increase the number of the pancreatic alpha cells and facilitate subsequent transition from hyperplasia to pancreatic neuroendocrine tumor (PNET), which is the only neoplasm known to occur in patients with mahvash disease. PNET and remarkable hyperglucagonemia without glucagonoma syndrome are clinical hallmarks of Mahvash disease. Mahvash disease is a rare autosomal recessive, familial, PNET. Based on the known frequency of two potentially inactivating exonal single nucleotide polymorphisms, it is estimated that the frequency of inactive glucagon receptormutation may occur at approximately 0.2%.