In addition to the histological diagnosis, alpha fetoprotein (AFP) and chorion gonadotropin (HCG) are used in clinical staging, therapy monitoring, and follow-up. Elevated markers without localization of metastases by imaging procedures are generally classified as progressive disease. However, other causes may be responsible for the elevated tumor markers: other malignant or benign diseases such as hepatocellular carcinomas, gastrointestinal tumors, bronchial carcinomas and benign diseases of the liver for AFP, and vesicular mole, hepatocellular, stomach, pancreatic and urothelial carcinomas for HCG. Moreover, technical disturbances in the modern sandwich assays with monoclonal antibodies are possible by heterophilic antibodies. These human anti-animal antibodies are built after immunoscintigraphy, immunostimulation and oral immunization by macromolecules. As a result, if progressive disease of a malignant germ cell tumor is unlikely, several steps have to be taken to determine the true causes for the elevated tumor markers before chemotherapy can be applied.