Uterine papillary serous carcinoma (UPSC) is a clinically aggressive and morphologically distinctive variant of endometrial carcinoma that has been recognized recently as a distinct entity. The association between radiation therapy (RT) and UPSC is rarely described in the literature. We describe the clinicopathologic features of a 71-year-old patient with UPSC that developed 15 years after radiation therapy for squamous cell carcinoma of cervix, stage IIB. In the subtotal hysterectomy specimen the endometrium was irregular with multifocally raised masses. Microscopically, the tumor was composed of high-grade papillary serous carcinoma focally admixed with solid transitional cell carcinomatous areas and multifocal intraepithelial carcinoma in adjacent atrophic endometrium. The tumor exhibited diffuse infiltrative growth with frequent lymphatic tumor emboli in the myometrium. Immunohistochemical staining for p53 and c-erbB-2 were positive in about 70% of the tumor cells. Carcinoembryonic antigen (CEA) was focally positive. Ki-67 positive cells were present in about 60% of the tumor cells. The tumor directly extended to the cervix and perirectal soft tissue and metastasized to the omentum. Intraoperative pelvic washing cytology was positive for papillary adenocarinoma cells. The possible etiologic role of radiation is discussed, and the literature on endometrial carcinomas developing after RT is reviewed.