Lipocalin 2 (LCN2) is a 25 kDa secreted protein, initially purified from neutrophil granules, and mainly expressed in immune cells, hepatocytes, renal cells, prostate, cells of the respiratory tract and cardiomyocytes. LCN2 belongs to the family of lipocalins known for their ability to traffic small hydrophobic molecules such as lipids and retinoids. Due to its ability to sequester iron-containing bacterial siderophores, LCN2 plays an essential part in the innate immunity as well as in the regulation of the cellular iron metabolism. Altered LCN2 expression occurs in di- verse pathological conditions, including kidney disease, obesity, steatohepatitis, inflammation and malignant transformation. In recent years, LCN2 gained attention as a potential biomarker in cancer as it is protease resistant and thus easily detectable in blood, urine, tissue and other body fluids. In line, numerous peer-reviewed reports established the LCN2 overexpression in cancers of diverse histological background. Apparently, LCN2 has contradictory roles in dif- ferent types of cancers. While it facilitates tumorigenesis by promoting survival, growth, inva- sion and metastasis, other studies report a negative correlation of LCN2 and disease outcome. Particularly, LCN2 suppression promoted cell proliferation, migration, invasion as well as the switch from epithelial to mesenchymal state. The underlying molecular mechanisms of the complex and ambiguous role of LCN2 in malignant tumor development and progression are not completely clarified yet. The following review focuses on major findings of LCN2 as a po- tential diagnostic and/or prognostic biomarker in prostate, lung and liver cancer, representing worldwide three of the cancers with the highest estimated incidence, mortality, and prevalence. In addition, we will highlight the progress of knowledge in understanding molecular pathways and regulation processes of LCN2 in those cancer types.