Early detection is the most effective way to improve the clinical outcome of malignancies. Although some tumor markers are now widely used in the clinic, their sensitivity and specificity are still not satisfactory. Thus, there is an urgent requirement for the discovery of new tumor markers. By measuring holistic endogenous metabolites, metabolomics can be used for delineating metabolic networks and discovering metabolic markers. Chromatography-mass spectrometry is the most widely used tool for metabolomics and has shown great potential for biomarker screening. In this review, the authors summarize: recent advances in the protocols and methodologies of chromatography-mass spectrometry-based metabolomics in the discovery of tumor markers; recently identified tumor metabolic markers for primary liver cancer, gynecologic cancer and genitourinary cancer and their applications; and commonly encountered problems in the translational research of metabolic markers.