Human chorionic gonadotropin (hCG)1 is a dimeric glycoprotein hormone consisting of noncovalently associated α and β subunits. It is produced principally by the trophoblastic cells of the placenta but may also be produced by nontrophoblastic tissues including normal pituitary and neoplastic cells. Therefore, qualitative and quantitative measurement of hCG is clinically useful in the diagnosis of normal and abnormal pregnancy and the management of patients with gestational trophoblastic disease (GTD) and other hCG-secreting malignancies. The measurement of hCG is complicated by its molecular heterogeneity in both structure and carbohydrate content. Multiple molecular variants of hCG are present in serum and urine and include intact hCG, nicked hCG (hCGn), free β-subunit hCG (hCGβ), nicked free β-subunit hCG (hCGβn), free α-subunit hCG (hCGα), and the β-core fragment hCG (hCGβcf). In addition, hCG is differentially glycosylated in various tissues, resulting in a range of molecular forms from hypoglycosylated to hyperglycosylated. So-called hyperglycosylated hCG (hCG-h) is probably the best known of these glycosylated variants. This molecular heterogeneity has led to numerous problems, including use of a nonstandard nomenclature for hCG variants, absence of purified standards to achieve accurate calibration, and discrepant characterizations of hCG variants that are recognized by different hCG immunoassays. This, in turn, has led to misunderstandings about which hCG immunoassays are appropriately used in different clinical scenarios. For example, although intact hCG is the principal variant in serum throughout most of pregnancy (1), hCG-h accounts for a relatively higher proportion of total hCG in the first several weeks of gestation (2), and hCGβ is present in much lower abundance (3). Although most trophoblastic tumors produce intact hCG, unusually increased concentrations of the other hCG variants (particularly hCGβ) can also be present (4). Finally, among germ cell tumors that produce hCG, 20%–40% produce hCGβ alone (5). In 1994, in an …