In epithelial ovarian cancer, solitary metastasis to and recurrences in the parenchyma of the spleen are rare in the absence of apparent disease in other sites. We report four patients who developed isolated, solitary splenic parenchymal recurrences of their epithelial ovarian adenocarcinomas and underwent a splenectomy to remove the recurrent disease. They had undergone optimal cytoreductive surgery for stage III grades 2-3 serous cystadenocarcinoma of the ovary, followed by six to nine cycles of cisplatin and cyclophosphamide chemotherapy and a negative second-look laparotomy. Evidence of relapse developed 2, 4, 6, and 10 years after initial treatment. In two patients, a rising CA-125 heralded the recurrence that was subsequently documented by computed tomography (CT) of the abdomen and pelvis with a single defect noted only in the splenic parenchyma. Two others had only a defect on CT scan. Based on these findings, the otherwise healthy women underwent an exploratory laparotomy, each had a single focus of recurrent poorly differentiated disease that was found in the splenic parenchyma and a splenectomy was performed. Multiple biopsies and cytologies revealed no other evidence of microscopic disease. There was no major postoperative morbidity. Subsequently, one woman was treated with intraperitoneal cisplatin, two with intravenous carboplatin, and one declined further therapy. Three women are alive and free of disease at 6 months to 3 years. The fourth woman is alive with recurrent disease near the site of the resected spleen found 10 months postsplenectomy. Thus, splenic recurrence of epithelial ovarian cancer can occur in the absence of other demonstrable metastasis, and it can be preceded by elevation of CA-125 and an abnormal CT scan. Based on this limited experience with selected patients, splenectomy may have a role in the management of this unusual recurrence.