Genetic mutations in the PTEN tumor suppressor gene are often found in malignant human cells, and these changes in the genome are especially characteristic of endometrial cancer. The results of our previous studies indicate the possibility of an alternative epigenetic mechanism of PTEN inactivation in endometrial cancer via methylation of its promoter region. In addition, evidence for the participation of PTENP1 pseudogene in positive regulation of the PTEN gene expression has been recently published. Taking into account these facts, the methylation status of the minimal promoter of the tumor suppressor gene PTEN and the 5′-terminal sequence of its pseudogene PTENP1 in endometrial cancer and hyperplasia was investigated by various methods. It was found that the DNA of PTEN gene studied was not methylated. At the same time, the PTENP1 pseudogene region was methylated in more than 50% of cases in endometrial cancer (11/18) and hyperplasia (5/9), but not in most normal tissues studied. We assume that methylation of pseudogene sequences can inhibit its usually observed transcription, and in accordance with the concept of competing endogenous mRNAs (ceRNAs) may be accompanied by suppression of the PTEN gene expression by the mechanism of RNA interference. Thus, aberrant suppression of the PTENP1 transcription may contribute to the pathogenesis of endometrial cancer. © 2013 Pleiades Publishing, Ltd.