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High-risk, early-stage endometrial cancer is optimally treated by hysterectomy followed by adjuvant radiotherapy. In 1%-9% of cases, the patient is medically unfit or personally unwilling to undergo primary surgery, and definitive radiotherapy may be offered as an alternative definitive therapy. Although several series have reported excellent intrauterine control and disease-specific survival for endometrioid histology, few outcome data are available for patients with serous or clear cell histology treated with radiotherapy alone. We herein describe one case each of early-stage, medically inoperable serous/clear cell histology endometrial cancer treated with definitive radiotherapy. Treatment was well tolerated by both patients, and neither patient required a treatment break. Acute toxicity consisted of self-limited cystitis in one patient. One patient was without evidence of disease progression at 54 months after radiotherapy.