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Retrorectal cystic hamartomas are rare congenital presacral lesions and malignancy is extremely rare. Although surgical excision is the essential for treatment, a unique feature of our case compared with previously reported tailgut cysts is that this patient's blood irregular antibodies are positive with higher operational risks.A 44-year-old woman presented to our department complaining of pelvic and perineal pain for 6 months. Computed tomography (CT) scan of the abdomen and pelvis demonstrated a well-demarcated hypodense, multilocular cystic lesion, 10 cm in size, in the presacral region of the right of the midline. We found her blood irregular antibodies were positive in the preoperative examination. So she quitted surgery. Exploratory laparotomy and incision and drainage of pelvic tumor were operated. Postoperative routine pathology showed: (retroperitoneal tumors) moderately differentiated adenocarcinoma. Combined with clinical symptom and imaging, malignant transformation of retrorectal cystic hamartomas (tailgut cysts) was diagnosed. Taking into account that cyst is not sensitive to radiotherapy, so tumor necrosis factor (TNF) and raltitrexed were infused into the cysts and 3 cycles oxaliplatin (130 mg/m2) were completed. Now although the lesion is shrink, but yellow, viscous mucus still secrete constantly, 100 ml/w.Given surgical excision is the essential for treatment, complete surgical excision should be implemented as far as possible. But if surgery cannot be carried out like the presented case, systemic chemotherapy and local radiotherapy are also available, which can alleviate the symptoms of oppression and improve the quality of life partly.