The architecture of the cell nucleus in cancer cells is often altered in a manner associated with the tumor type and aggressiveness. Therefore, it has been the central criterion in the pathological diagnosis and prognosis of cancer. However, the molecular mechanism behind these observed changes in nuclear morphology, including size, remains completely unknown. Based on our current understanding of the physiology of the nuclear pore complex (NPC) and its constituents, which are collectively referred to as nucleoporins (Nups), we discuss how the structural and functional ablation of the NPC and Nups could directly or indirectly contribute to the changes in nuclear size observed in cancer cells.