The purpose of this prospective clinical trial was to determine the reliability of the Pipelle endometrial biopsy instrument in recovering adequate tissue for confirmation of the diagnosis of endometrial cancer in patients with known endometrial carcinoma, and to compare endometrial histology of the sampling specimen with that of the subsequent hysterectomy specimen. Forty patients were enrolled in this study. All biopsies were performed in the office without anesthesia. The patients had a median age of 62 years (range 40-83). Discomfort was reported by the patient as mild, moderate, or severe; only two patients (5.0%) reported severe pain. There were no complications experienced with endometrial sampling. Thirty-nine of 40 specimens (97.5%) confirmed endometrial carcinoma; therefore, this study yielded a 97.5% sensitivity for the Pipelle endometrial sampling device. Comparing Pipelle and hysterectomy histology for individual patients, the histologic grade was the same in 29 (74.4%), while the Pipelle demonstrated a more advanced degree of differentiation in five (12.8%) and a lesser degree in five (12.8%). There was no residual tumor identified in one hysterectomy specimen (2.5%). Among the 12 patients who had a D&C for diagnostic purposes before referral, the Pipelle biopsy correlated with the D&C histology in ten of 12 (83.3%) and revealed a more advanced grade of tumor in one (8.3%) and a more differentiated grade in one (8.3%). In one patient, the D&C histology was adenocarcinoma grade 1, with the Pipelle demonstrating atypical hyperplasia and the hysterectomy specimen interpreted as endometrial adenocarcinoma in situ. This study demonstrates the Pipelle to be an accurate device for endometrial sampling in patients with endometrial carcinoma.