Abstract
Sex differences in cellular and systems biology have been evolutionarily selected to optimize reproductive success in all species with little (sperm) and big (ova) gamete producers. They are evident from the time of fertilization and accrue throughout development through genetic, epigenetic, and circulating sex hormone-dependent mechanisms. Among other effects, they significantly impact on chromatin organization, metabolism, cell cycle regulation, immunity, longevity, and cancer risk and survival. Sex differences in cancer should be expected and accounted for in basic, translational, and clinical oncology research.