The last decade introduced a paradigm shift in molecular biology towards the recognition of non-protein-encoding RNA molecules as functionally important players in physiological and pathological processes. These transcripts are frequently deregulated in tumors and may also exert tumor suppressive or oncogenic functions. Our research aims at elucidating the expression, regulation and function of long non-coding RNAs in lung, liver and breast cancer. In detail, I will present our discovery of the lncRNA MALAT1 as a biomarker for lung cancer metastasis and the generation of a novel loss-of-function model in human cells unraveling the active function of MALAT1 as a regulator of gene expression governing lung cancer metastasis. We also provide the first global comprehensive map of long ncRNA expression in a broad range of human tumor and normal tissue samples and discovered many new lncRNAs associated with cancer as well as tissue-, histology- and prognosis-specific ncRNA signatures. First data shed light onto the important functions of these newly discovered lncRNAs at the cellular and molecular level.