Small nucleolar RNAs (snoRNAs) are emerging as an important new class of genes deregulated in cancer. Orphans snoRNAs are encoded outside of ribosomal protein genes and are involved in either gene splicing or are microRNA precursors. In this issue of JCI, Chu et al. find that ACA11, an orphan snoRNA encoded in an intron of the WHSC1 gene, is aberrantly overexpressed in t(4;14)-positive patients with multiple myeloma (MM), in which it influences growth of MM cells, resistance to chemotherapy, and oxidative stress. These findings represent the first identification of a snoRNA overexpressed as a consequence of a chromosomal translocation, a potent driving force of the neoplastic process in general and hematopoietic malignancies in particular.