Hypoglycemia in patients without diabetes is a diagnostic challenge for the endocrinologist. Sometimes it is related to rare causes such as Doege–Potter Syndrome (DPS). DPS is caused by an abnormal insulin-like grow factor 2(IGF-2) that retains part of the E domain during the production process, resulting in a longer peptide called “big-IGF-2”. We present a case report of DPS with emphasis on the diagnosis and especially on the difficulties in interpreting the biochemical findings. An elderly patient with an intrathoracic neoplasm and hypoglycemia underwent various tests: insulin autoantibodies and fasting test were both negative. She had low values of IGF-1 and normal values of IGF-2 that apparently excludes a diagnosis of DPS. The evaluation of the IGF-2/IGF-1 ratio is the most important test because a ratio >10 is widely considered to be indicative of non-islet cell tumor hypoglycemia (NICTH). Glucose infusion and steroid therapy were used to control the hypoglycemia, but the definitive treatment was surgery, which almost immediately reversed the hypoglycemia. The differential diagnosis of hypoglycemia should include rare causes such as DPS, and the IGF-2/IGF-1 ratio is a useful tool.