Chromogranin A (CgA) is gaining acceptance as a serum marker ofud neuroendocrine tumors. Its specificity in differentiating betweenud neuroendocrine and nonneuroendocrine tumors, its sensitivity to detectud small tumors, and its clinical value, compared with other neuroendocrineud markers, have not clearly been defined, however. The objectives of thisud study were to evaluate the clinical usefulness of CgA as neuroendocrineud serum marker. Serum levels of CgA, neuron-specific enolase (NSE), and theud alpha-subunit of glycoprotein hormones (alpha-SU) were determined in 211ud patients with neuroendocrine tumors and 180 control subjects withud nonendocrine tumors. The concentrations of CgA, NSE, and alpha-SU wereud elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors,ud respectively. Serum CgA was most frequently increased in subjects withud gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%),ud nonfunctioning tumors of the endocrine pancreas (69%), and medullaryud thyroid carcinomas (50%). The highest levels were observed in subjectsud with carcinoid tumors. NSE was most frequently elevated in patients withud small cell lung carcinoma (74%), and alpha-SU was most frequently elevatedud in patients with carcinoid tumors (39%). Most subjects with elevatedud alpha-SU levels also had elevated CgA concentrations. A significantud positive relationship was demonstrated between the tumor load and serumud CgA levels (P < 0.01, by chi 2 test). Elevated concentrations of CgA, NSE,ud and alpha-SU were present in, respectively, 7%, 35%, and 15% of controlud subjects. Markedly elevated serum levels of CgA, exceeding 300ud micrograms/L, were observed in only 2% of control patients (n = 3)ud compared to 40% of patients with neuroendocrine tumors (n = 76). Weud conclude that CgA is the best general neuroendocrine serum markerud available. It has the highest specificity for the detection ofud neuroendocrine tumors compared to the other neuroendocrine markers, NSEud and alpha-SU. Elevated levels are strongly correlated with tumor volume;ud therefore, small tumors may go undetected. Although its specificity cannotud compete with that of the specific hormonal secretion products of mostud neuroendocrine tumors, it can have useful clinical applications inud subjects with neuroendocrine tumors for whom either no marker is availableud or the marker is inconvenient for routine clinical use