NPM1 is a crucial gene to consider in the context of the genetics and biology of cancer. NPM1 is frequently overexpressed, mutated, rearranged and deleted in human cancer. Traditionally regarded as a tumour marker and a putative proto-oncogene, it has now also been attributed with tumour-suppressor functions. Therefore, NPM can contribute to oncogenesis through many mechanisms. The aim of this review is to analyse the role of NPM in cancer, and examine how deregulated NPM activity (either gain or loss of function) can contribute to tumorigenesis.