The lncRNA cancer susceptibility candidate 2 (CASC2) has been initially discovered in a genomic area on 10q26 that is commonly lost in human endometrial cancer. Subsequent assessments revealed its down-regulation in almost all kinds of cancer including glioma, breast cancer, colorectal cancer, lung cancer, ovarian cancer and hepatocellular carcinoma. Yet, it has been shown to be up-regulated in astrocytoma and in paclitaxel (PTX) resistant breast cancer tissues. In vitro studies have shown the role of this lncRNA in suppression of cell proliferation and induction of apoptosis. Animal studies have shown that over-expression of CASC2 suppresses tumorigenesis of human cancer cells in xenograft models. Diagnostic power of CASC2 levels has been evaluated in a number of human cancers and the best parameters have been demonstrated in pituitary adenomas and oral squamous cell carcinoma. Taken together, the main body of evidence show a tumor suppressor role of CASC2 and indicate up-regulation of this lncRNA as a putative therapeutic modality for human cancers. In this review, we summarize the data regarding expression pattern, function and diagnostic role of CASC2 in human cancer based on the results of cell line studies, animal investigations and human studies.