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This study was aimed at analyzing alterations in K-ras gene and SMAD4 gene promoter in endometrial carcinoma tissue in Serbian patients.The study has encompassed 36 patients whose endometrial cancer tissue samples and peripheral blood samples were analyzed for the presence of alterations in the K-ras gene and the SMAD4 gene promoter. The detection of K-ras codon 12 mutation was performed by polymerase chain reaction restriction fragment length polymorphism technique. Analysis of mononucleotide repeat variants at -462T(15) and -4T(12) of the SMAD4 gene promoter was performed by capillary electrophoresis analysis of DNA fragments fluorescently labeled by polymerase chain reaction.Mutation in codon 12 of the K-ras gene was detected with relatively high frequency of 75.0% (27 of 36 cases). Analysis of 2 mononucleotide repeats in the SMAD4 gene promoter showed that in most cases, haplotypes -462T(15)/-4T(12) and -462T(16)/-4T(12) were present; whereas in one case, a novel haplotype -462T(15)/-4T(10) was detected.Findings on the role and potential significance of the K-ras codon 12 mutation and SMAD4 gene promoter variants in patients with endometrial carcinoma remain controversial, and their occurrence in this type of cancer should be further investigated.