Neuron-specific enolase (NSE) is a glycolytic enzyme that catalyzes the conversion of phosphoglycerate to phosphoenolpyruvate and is the dominant enolase-isoenzyme found in neuronal and neuroendocrine tissues. NSE expression occurs in small cell lung cancer, neuroblastoma, neuroendocrine tumors, and events resulting in brain damage. NSE is currently used to monitor disease progression and management in small cell lung cancer, neuroblastoma, and select events of brain damage resulting from ischemic stroke. Assays for NSE are based on the antibody sandwich principle using ELISA or CLIA. They can be affected by false low results in the presence of extremely high NSE concentrations or autoantibodies to NSE and false results in the presence of heterophile antibodies.