Objective: To determine the percentage of endometrial hyperplasia positive for p53 expression in both spontaneously occurring cases or following the use of unopposed estradiol. Methods: Fifty-four postmenopausal patients with endometrial hyperplasia diagnosed by endometrial biopsy and hysteroscopy were recruited to this study. Thirty-three patients had used unopposed estradiol for periods of time from I to 3 years. P53 expression was detected in paraffin-embedded endometrial specimens by immunohistochemical methods. Results: The percentage of endometrial hyperplasia positive for p53 expression was significantly greater in spontaneously occurring hyperplasia than in cases induced by the unopposed use of estradiol. Conclusion: Endometrial hyperplasia caused by the unopposed use of estradiol during menopause probably harbors fewer genomic errors than those cases occurring spontaneously. (C) 2003 Published by Elsevier Science Ireland Ltd.