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Liquid-based cytology represents an opportunity to re-evaluate endometrial cytology. We evaluated the accuracy of liquid-based endometrial cytology as compared to biopsy in 670 women scheduled for histeroscopy because of thickened endometrium (>4 mm), as evaluated by transvaginal sonography. Endometrial biopsy detected pathology in 41 (6%) of cases (21 of which were adenocarcinomas). Cytologic study found pathology in 62 (9%) cases (19 of which were adenocarcinomas). Two hundred ninety-one biopsies (43%) and 28 (4%) cytologies were inadequate. The sensitivity and the specificity were estimated, respectively, at 95% and 98%; the positive and negative predictive values were estimated, respectively, at 83% and 99%. Cytology provided sufficient material more often than biopsy (P < 0.01). We consider endometrial cytology an efficacious diagnostic opportunity. It could be usefully applied in association with transvaginal sonography. The combination of these procedures might reduce more invasive and expensive diagnostic procedures.