Objectives: The aim of the study was to evaluate transcription activity of melatonin receptors and genes associated with regulation of their activity in endometrial adenocarcinoma to identify probable diagnostic and prognostic molecular markers. Material and methods: The material included endometrial adenocarcinoma tissue samples of histopathological grades G1, G2, G3, and normal endometrium. The molecular analysis was performed on 37 patient samples. Total RNA was extracted and used for the microarray HG-U133A analysis. Among 22 283 ID mRNA, only entities of genes associated with regulation of melatonin receptors activity were selected. qRT-PCR was employed for validation, what allowed to compare melatonin receptor genes activation in endometrial cancer tissues to the normal endometrium. Results: The results of the microarray experiments showed that only 18 ID mRNA were differential in endometrial cancer samples as compared to the control at p-value<0.05 and FC(log2)>1.5. These genes were identified as differentially expressed in grade G2- ASMTL, GNA11, PER2, PTGDS and in grade G3- GNAI2, GNA11. Silencing of RGS4 encoding RGP4, which regulates signal transmission by G protein, was observed in all cancer groups, independently of the histopathological grade. Conclusions: The profile expression of genes associated with regulation of melatonin receptors activity was different and dependent on the histopathological grade of endometrial cancer and can be an additional diagnostic and prognostic marker. Statistically significant was the down-regulation of melatonin biosynthesis genes (ASMTL) and melatonin signal transmitters (GNA11, GNA12, RTGS