While the pathogenesis of varicose veins is assumed to be multifactorial, including the aging process, the etiology, especially in the very young, is strongly linked to genetics and is believed to be associated with improper development and regulation of venous tissue maturation. The aim of this study was to identify the genes whose expression is different in primary varicose veins compared to normal veins in the legs. To test this hypothesis, the differentially expressed gene technique was performed on a large-scale screen of mRNA from varicose and normal veins. Transcriptional products corresponding to cDNA were compared between the two vein types, and one gene showed the greatest differential expression between the samples in all sets of experiments, confirmed by reverse-transcriptase polymerase chain reaction. Octamer-binding transcription factor-1 gene (Oct-1) was upregulated in primary varicose veins. Therefore, we suggest that Oct-1 may play an important role in the development of primary lower extremity varicose veins.