Abnormal uterine bleeding is a frequent medical concern for premenopausal and postmenopausal patients. Endometrial biopsy is a safe, cost-effective option offered in the office setting. Although endometrial biopsy may result in insufficient tissue or false-negative results, data suggest that endometrial biopsy is 90% sensitive for endometrial cancer and 82% sensitive for atypical hyperplasia, with specificity of 100% for postmenopausal patients and similar results in premenopausal patients. Topical cervical analgesia and oral nonsteroidal anti-inflammatory drugs decrease a patient’s discomfort during endometrial biopsy. Aftercare instructions and how patients want to receive results should be reviewed in advance of performing the endometrial biopsy.