Glucose metabolism represents a complex system, and several components of the regulatory metabolic pathways may induce abnormalities in cellular growth and regulation. The strongest evidence of an association between glucose metabolism alterations and cancer derives from cohort studies, showing increased cancer incidence and mortality in the presence of diabetes. In particular, several studies clearly indicate an association between type 2 diabetes and the risk of colorectal, pancreatic, and breast cancer. An increased risk of liver, gastric, and endometrial malignancies has also been suggested. Type 1 diabetes is associated with an elevated risk of female reproductive organs and gastric cancers. The risk of malignancies is also increased at earlier stages of glucose metabolism abnormalities, with a linear relationship between cancer risk and plasma insulin levels, usually elevated in the presence of metabolic syndrome or diabetes. The prevalence of diabetes and obesity is rapidly increasing worldwide; if these conditions are associated even with a small increase in the risk of cancer, this will translate into important consequences for public health.