Immunohistochemical markers to assist in the diagnosis and classification of hyperplastic endometrial epithelial proliferations would be of diagnostic use. To examine the possible use of PAX2 as a marker of hyperplastic endometrium, cases of normal endometrium, simple and complex hyperplasia without atypia, atypical hyperplasia, and International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrioid carcinomas were stained for PAX2. Two hundred and six endometrial samples were available for interpretation of PAX2 staining. The percentage of cases with complete PAX2 loss (0% of cells staining) increased with increasing severity of hyperplasia: 0% of normal proliferative and secretory endometrium (n=28), 17.4% of simple hyperplasia (n=23), 59.0% of complex hyperplasia (n=83), 74.1% of atypical hyperplasia (n=54), and 73.3% of FIGO grade 1 endometrioid cancers (n=15). Partial loss of PAX2 expression did occur in normal endometrium (17.9%) but in smaller proportions of tissue and was less frequent than in simple hyperplasia (47.8% with partial loss), complex hyperplasia (32.5%), atypical hyperplasia (22.2%), and FIGO grade 1 carcinomas (20.0%). Uniform PAX2 expression was rare in complex (8.4%) and atypical hyperplasia (3.7%) and carcinoma (6.7%). When evaluating loss of PAX2 in histologically normal endometrium adjacent to lesional endometrium in a given case, statistically significant differences in staining were observed for simple hyperplasia (P=0.011), complex hyperplasia (P<0.001), atypical hyperplasia (P<0.001), and FIGO grade 1 endometrioid cancer (P=0.003). In summary, PAX2 loss seems to occur early in the development of endometrial precancers and may prove useful in some settings as a diagnostic marker in determining normal endometrium from complex and atypical hyperplasia and low-grade carcinomas. However, it is not useful in distinguishing between these diagnostic categories.