Human pituitary tumor-transforming gene 1 (PTTG1) is a newly identified proto-oncogene, and its overexpression occurs in a wide variety of human cancers. The tumor suppressor gene phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is frequently mutated or deleted in numerous tumors, especially in endometrial carcinoma. The aim of this study was to investigate whether the aberrant expression of PTTG1 and PTEN is associated with tumorigenesis and progression of endometrial carcinoma. Tissue microarray and immunohistochemical staining were undertaken in 124 endometrial carcinoma, 28 atypical hyperplasia and 35 normal endometrium samples. Then, the correlation of PTTG1 and PTEN expression with the clinicopathological features and with the levels of estrogen and progesterone receptor was analyzed. The presence of PTTG1 and PTEN protein was significantly increased and decreased, respectively, as lesions progressed from normal endometrium to atypical hyperplasia to carcinoma. PTTG1 protein showed a significantly positive correlation with TNM stage, but not with other characteristics. In addition, PTEN protein did not correlate with any parameters except for histological grade, to which it was found to be inversely related. Statistical analysis confirmed a significant relationship between an increase in PTTG1 and a decrease in PTEN. These results indicate that high expression of PTTG1 and low expression of PTEN may be involved in pathogenesis and development of endometrial carcinoma. The findings also provide evidence that combined evaluation of the two markers may be useful in predicting tumor behavior and thus prognosis.