The C19MC miRNA cluster region comprises 46 micro RNA genes which encode for large polycistronic microRNAs (miRNA). C19MC amplifications have been reported in tumor entities, such as breast cancer and parathyroid carcinomas. According to the 2016 WHO classification of tumors of the central nervous system, amplification of this region defines a new entity of embryonal tumors with multilayered rosettes (EMTR), C19MC-altered. Amplification of C19MC leads to an overexpression of miRNAs in this cluster region that drive cell proliferation, promote cell survival, and increase carcinogenicity of cells providing functional evidence that C19MC miRNAs act as oncogenes. ETMR with C19MC miRNA cluster amplification are rare brain tumors which occur primarily in infants and young children showing a poor overall survival. Hence, detection of C19MC miRNA cluster amplification by Fluorescence in situ Hybridization may be of diagnostic and prognostic relevance.