Objective. To determine the prevalence of focally growing lesions in the uterine cavity in women with postmenopausal bleeding and endometrium greater than or equal to5 mm and the extent to which such lesions can be correctly diagnosed by D&C. Methods. In a prospective study, 105 women with postmenopausal bleeding and endometrium greater than or equal to5 mm at transvaginal ultrasound examination underwent diagnostic hysteroscopy, D&C and hysteroscopic resection of any focally growing lesion still left in the uterine cavity after D&C. Twenty-four women also underwent hysterectomy. If the histological diagnosis differed between specimens from the same patient, the most relevant diagnosis was considered the final one. Results. Eighty percent (84/105) of the women had pathology in the uterine cavity, and 98% (82/84) of the pathological lesions manifested a focal growth pattern at hysteroscopy. In 87% of the women with focal lesions in the uterine cavity, the whole or parts of the lesion remained in situ after D&C. D&C missed 58% (25/43) of polyps, 50% (5/10) of hyperplasias, 60% (3/5) of complex atypical hyperplasias, and 11% (2/19) of endometrial cancers. The agreement between the D&C diagnosis and the final diagnosis was excellent (94%) in women without focally growing lesions at hysteroscopy. Conclusion. If there are focal lesions in the uterine cavity, hysteroscopy with endometrial resection is superior to D&C for obtaining a representative endometrial sample in women with postmenopausal bleeding and endometrium greater than or equal to5 mm.