Through this Notice of Scientific Interest (NOSI), the National Cancer Institute intends to stimulate research on the role of RNA modifications in the area of cancer biology. Despite the recognition that RNA modifications and editing exert a substantial impact on gene expression and function, there is a lack of mechanistic insights into the dynamic regulation of RNA modifications and their de-regulation as drivers of cancer formation. A better understanding of the extent, variety, and crosstalk between different types of RNA modification, and the elucidation of the molecular players that read and interpret the modification code are needed to reveal the mechanisms of RNA modifications that underly cancer formation and the cancer phenotype.