T he "specialized ribosome" concept proposes that ribosome variants are produced and differentially regulate translation. Examples supporting this notion demonstrated heterogeneity of ribosomal protein composition. However , ribosome translational activity is carried out by rRNA. We, and others, recently showed that rRNA heterogeneity regulates translation to generate distinct translatomes promoting tumorigenesis. Translation is one of the last steps of gene expression, during which ribosomes synthesize proteins. A growing body of evidence indicates that the translation process per se plays a key role in tumorigene-sis. 1 Significantly, it was recently revealed that components of the translational machinery play unexpected direct roles in tumorigenesis. For example, haploinsuffi-ciency in ribosomal protein (RP) RPL24 is sufficient to significantly delay tumori-genesis in mice overexpressing the onco-gene C-Myc or lacking the tumor suppressor phosphatase and tensin homo-log (PTEN). 1 In addition, it has been extensively demonstrated that the expression of oncogenes and tumor suppressors is regulated at the protein synthesis level. 1,2 Finally, the specific inhibition of RNA polymerase I (RNA pol I) using small molecules selectively kills cancer versus healthy cells in mouse models. 3