Human chorionic gonadotropin (hCG) is not a single biological molecule. There is the regular form of hCG produced by differentiated syncytotrophoblast cells (regular hCG). This hormone primarily functions to maintain the myometrial and decidual spiral arteries, or the vascular supply of the placenta during the full course of pregnancy. Hyperglycosylated hCG is made by undifferentiated cytotrophoblast cells, which are extravillous cytotrophoblast cells. This is an autocrine with separate functions, it maintains trophoblast invasion as in implantation of pregnancy and malignancy in gestational trophoblastic diseases. A hyperglycosylated free beta-subunit is produced by a high proportion of all malignancies. This also functions as an autocrine by promoting the growth and invasion of the malignancy. When ordering an hCG test it is important to realize what is being measured and whether the test ordered will detect appropriately these three variants of hCG as well as their degradation products. Most automated commercial laboratory tests, point-of-care tests and over-the-counter tests are limited in what they detect, focusing only on regular hCG. This is in part due to the US FDA, who only consider regular hCG as part of a pregnancy test, and to whom only detection of regular hCG is necessary. This may cause test errors since primarily hyperglycosylated hCG is produced in early pregnancy and in choriocarcinoma and germ cell testicular malignancies. Only free beta-subunits may be produced in other germ cell malignancies (all applications for hCG test). The exceptions are the older style hCGb radioimmunoassay and the Siemens Immulite platform hCG test, which detect all beta-subunit variants of hCG and their degradation product appropriately. Apart from test specificity limitations, assays for hCG and its variants are widely used clinically in pregnancy detection, early pregnancy detection, prediction of spontaneously aborting, and ectopic pregnancies and prediction of trisomy pregnancies. hCG tests are essential in managing gestational trophoblastic diseases, whether hydatidiform mole, invasive mole or choriocarcinoma, and are very useful in management of testicular malignancies and other germ cell malignancies.