Carcinogenesis is a multistep process resulting from mutations in genes controlling the cellular growth, differentiation, apoptosis, and genome integrity maintenance. We investigated relationships between the PTEN and MLH1 immunoreactivity in the cancer cells and the histological subtypes of endometrial carcinoma as well as the survival times of the affected women. The PTEN and MLH1 protein immunoexpression was also examined separately in both clinicopathological groups of endometrial carcinoma. We estimated the practical use of the proteins as diagnostic and predictive markers. The histoclinical analysis was performed on 104 patients. The follow-up in all the cases was well known. To assess the expression of both proteins in the cancer cells we adopted a semiquantitative immunohistochemical analysis. We proved that the incidence of the PTEN and MLH1 nuclear positive cells was significantly higher in the serous type than in the endometrioid one. We also demonstrated a strong correlation between both cytoplasmic and nuclear PTEN immunoexpression and the survival times in the entire cohort. In conclusion, the PTEN and MLH1 immunohistochemical analysis broadens the microscopic diagnosis of the endometrial carcinomas. However, the PTEN and MLH1 antibodies tests cannot determine the recognition of the cancer, and they should not be regarded as independent prognostic factors.