MicroRNAs (miRNAs) are short—20 to 23 nucleotides— nonprotein-coding RNAs that regulate the expression of protein-coding genes. miRNA function is principally determined by the seed region, critically consisting of nucleotides at positions 2 to 7 (2 to 7nt), which binds to one or more complementary sequences in the 39-untranslated region of mRNA targets. In man, there are more than 1,000 mature miRNAs, each of which can target many different mRNAs, whereas, conversely, each individual mRNA can be suppressed by multiple miRNAs. There is therefore an extensive network of miRNA-mediated control of mRNA abundance and translation, which regulates fundamental cellular processes including development, homeostasis and proliferation. Dysregulation of miRNA expression plays a key role in tumorigenesis, with miRNAs acting as both oncogenes when overexpressed or as tumor suppressor genes when underexpressed. Of interest, miRNA profiles in individual tumor types reflect the developmental lineage of the cells of origin. Some cancers have clear signatures of circulating miRNAs that offer potential for improving diagnostic tests in clinical oncology practice. In the report that accompanies this article, Dieckmann et al extend previous observations on the value of circulating miRNAs as a new generation of biomarkers for malignant germ cell tumors (GCTs).