Heterophilic antibodies in an immunoassay can lead to false positive reaction. This is especially problematic, when substances are tested which are present only under certain conditions, e.g. human chorionic gonadotrophin (hCG). False positive detection of hCG can lead to medical or invasive surgical treatments. Here we report the case of a female patient with persisting hCG titres in the range of 200 U/I, leading to laparoscopy and methotrexate treatment. Other cases in the literature are reported. Guidelines are discussed on how those cases can be avoided in future.