Primary retroperitoneal serous adenocarcinoma is an extremely rare clinical entity, with only five cases previously reported. We describe a 66-year-old woman with serous adenocarcinoma arising from the retroperitoneum, adhesive to the ileocecum. On MRI, the tumor was 17 × 10 × 6 cm in size and monocystic. The tumor cells were positive for CA125, estrogen receptor, and Wilms tumor 1, and were differentiated from enterogenic cyst by the presence of cytokeratin 7 (+), and the absence of cytokeratin 20 (−). Simultaneously, uterine adnexal serous adenocarcinoma was detected. The volume of the retroperitoneal tumor was 14 times larger than that of the uterine adnexal tumor. We suggest the possibility that the retroperitoneal cancer arose as a primary cancer from rests of the müllerian epithelium synchronously with the uterine adnexal cancer. The patient had been taking conjugated estrogen for 10 years, suggesting that long-term estrogen stimulation may have contributed to the progression of the tumors.