Endometrial carcinomas show frequent PTEN-PI3K pathway abnormalities, and there are currently multiple trials focused on PI3K pathway inhibitors in patients with endometrial carcinoma. PTEN immunohistochemistry may help to select patients with potential for response to targeted therapy, making it important to develop and validate this stain in formalin-fixed, paraffin-embedded tissue. Immunohistochemistry for PTEN was performed and scored independently on 118 cases of endometrial carcinomas from 2 cancer centers using monoclonal DAKO 6H2.1 antibody. Cases were scored as positive, negative, or heterogeneous; reproducibility of PTEN staining and interpretation was assessed. Overall interobserver agreement was good (weighted κ=0.80), with 82% concordance, similar for nonendometrioid (81%) and endometrioid carcinomas (85%). Twenty-one of 118 cases showed discrepant results (17%) that resulted from differences in interpretation and not staining. Our study shows that evaluation of PTEN loss by immunohistochemistry is highly reproducible with the application of standard immunohistochemical techniques and simple scoring criteria.