RNAs are intrinsic components of the translational apparatus, rRNA, tRNA, and mRNA. For many years it has been accepted that translational regulation proceeds via mRNA cis-regulatory elements and protein factors. Recently, trans-acting regulatory factors made of RNA have been identified as major regulators of translation. RNAs are mainly composed of four ribonucleotides. However, a variety of modified nucleotides, methylated or pseudouridylated, are found in all types of RNAs. These nucleotide modifications occur posttranscriptionally and allow increasing the diversity of RNA composition and activity. These RNA modifications are part of epigenetic regulation of gene expression at the translational level and appear to be modified in cancer. Among alterations of RNA modifications observed in cancer, alterations of rRNA represent a prototypic example playing a central role in the pathological process. We describe the function of rRNA methylation in the context of the cancer process.