Recently several LH/hCG receptor-independent activities for human chorionic gondotropin (hCG) have been described, including activation of the TGF-β receptor (TGFβR) by hyperglycosylated hCG (hCG-h) and stimulation of trophoblast invasion. As the hCG concentrations used in these studies have been rather high, reflecting physiological hCG levels in pregnancy, even a minor contamination with growth factors, that act at very low concentrations, may be significant. Several commercial hCG preparation have been found to contain significant amounts of EGF, which we also confirmed here. Furthermore, we found that some hCG preparations also contain significant amounts of TGF-β1. These hCG preparations were able to activate extracellular signal-regulated kinases 1/2 (ERK1/2) in JEG-3 choriocarcinoma cells or TGFβR in mink lung epithelial cells transfected with a reporter gene for TGFβR activation. No such activation was found with highly purified hCG or its free β-subunit (hCGβ), irrespective of whether they were hyperglycosylated or not. Taken together, our results suggest that the growth factor contaminations in the hCG preparations can cause activation of TGFβR and, at least in JEG-3 cells, mitogen-activated protein kinase-signaling. This highlights the importance to carefully control for potential contaminations and that highly purified hCG preparations have to be used for biological studies.