Endometrial carcinoma is among the most frequently diagnosed gynecological malignancies in highly developed countries. Research has been conducted for 20 years to define the molecular pathology of this disease and much is already known, but adequate prognostic, diagnostic, and monitoring markers are still missing. Recently, mitochondrial research opened a new perspective. The participation of abnormalities of those organelles and mutations of the mitochondrial genome has been defined in some types of cancer and is still under investigation. MtDNA mutations are also found in endometrial adenocarcinoma, although their impact on cell physiology has not been determined so far. Some processes involving mitochondria are widely known and described in numerous papers. These include electron transport and apoptosis, but others await further research. A forward genetics approach has been used in a wide spectrum of projects in which cancer tissue samples were collected from subjects with defined diagnoses and metabolic abnormalities and mtDNA mutations were checked. Thanks to this approach, characteristic patterns of mitochondrial disruption have been assigned to specific types of cancer. This review focuses on the molecular characteristics of endometrial adenocarcinoma with special focus on mitochondrial abnormalities. Research on cancer molecular pathology in endometrial adenocarcinoma may lead to the development of specific screening and/or diagnostic markers.