Glucose intolerance and insulin resistance are among the leading risk factors for breast (BC) and endometrial cancer (EC). Differences in the degree of association of these endocrine disorders with BC and EC can at least partly be explained by the diverse polygenic nature of the aforementioned metabolic shifts as well as of oncological diseases themselves. In 105 healthy postmenopausal women and 301 female cancer patients (110 BC and 191 EC) without overt diabetes mellitus, we compared the frequencies of the following genetic polymorphisms: insulin receptor substrate-1, IRS Gly972Arg; leptin receptor, LEPR Lys109Arg and Gln223Arg; mitochondrial uncoupling protein-2, UCP2_866G/A; and the ND3 gene of mitochondrial DNA, mtDNA 10398A/G. Genotyping was performed by allele-specific real-time PCR. The heterozygous genotype Gln/Arg of the Gln223Arg polymorphism in LEPR and the combination of the Gln/Arg and Gln/Gln genotypes proved to be associated with elevated risks of both BC (OR_Gln/Arg = 2.03 (CI = 1.08-3.81), p = 0.027; OR_{Gln/Arg+Gln/Gln} = 1.87 (CI = 1.02-3.43), p = 0.042) and EC (OR_Gln/Gln = 2.05 (CI = 1.00-4.17), p = 0.046, OR_Gln/Arg = 1.88 (CI = 1.07-3.28), p = 0.026). Other markers (genotype UCP2_866AA and mtDNA polymorphism 10398A) appeared to be relatively more frequent in EC than in BC, which may account for lower insulin sensitivity and higher incidence of carbohydrate metabolism disorders in EC cases.