Endogenous hyperinsulinemic hypoglycemia (EHH) is an uncommon disease characterized by inappropriately high plasma insulin levels despite low plasma glucose levels. Some rare etiologies can lead to EHH. Correct diagnosis is a prerequisite for treatment. Hence, although challenging, it is crucial for patients with EHH to identify the different causes. We describe a case series of three patients, all of whom had obvious hypoglycemic symptoms and extraordinary hyperinsulinemia. Their plasma glucose, insulin, and C-peptide levels were tested simultaneously when hypoglycemia occurred. Moreover, other biochemical indices and relevant antibody levels were measured and imaging examinations were conducted. According to their medical history, physical examination, laboratory results, and imaging findings, the three patients were diagnosed with insulinoma, type B insulin resistance syndrome, and insulin autoimmune syndrome. After precise treatments, hypoglycemia was ultimately eliminated. Although these diseases have similar symptoms and biochemical abnormalities, the treatment and prognosis are different. The case series presented here highlights the challenges in the differential diagnosis of EHH. An accurate diagnosis is necessary for hypoglycemia treatment.