The incidence and mortality of different types of cancer are associated with specific gender differences. Gender differences in cancer epidemiology are one of the most significant findings. Men are more affected by cancer death, especially from hematological malignancies. The gender difference in cancer incidence is due to regulation at the genetic and molecular level and sex hormones, such as estrogen. At the genetic and molecular level, gene polymorphisms and differences in drug metabolism generate differences in cancer incidence between men and women. Sex hormones modulate gene expression in various cancers. Genetic or hormonal differences between men and women determine the effect of chemotherapy. To date, animal studies and clinical trials investigating chemotherapy have shown gender differences. The use of chemotherapy without considering gender differences may lead to a discrepancy between efficacy and toxicity between the two sexes. Based on available scientific evidence supporting gender differences in chemotherapy, all cancer clinical trials should consider gender differences in cancer incidence and mortality, genetic and molecular basis of cancer, sex hormones in cancer incidence, and efficacy and toxicity of chemotherapy. Cancer incidence and mortality rates are higher in men than in women. Cancers of the bladder, stomach, liver and leukemia are diagnosed more often in men than in women. Lung and stomach cancer, the leading causes of cancer death, show higher mortality rates in men than in women. Male-specific cancers such as prostate cancer are also a prominent cause of cancer death. In patients with colorectal carcinoma, women develop the malignancy on the right side, while men develop the disease more on the left side. Right-sided colon cancer is associated with greater severity than cancer that develops on the left side. The reason for the differences in location may be due to differences in the level of estrogen between men and women. Bibliography: Anderson GD. Sex and racial differences in pharmacological response: where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality.