A 14-year-old female with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency underwent bilateral adrenalectomy at 6 years of age as a result of poor hormonal control. Because the patient was adrenalectomized, extra adrenal androgen production was suspected. Imaging studies including pelvic ultrasound and pelvic magnetic resonance imaging (MRI) were obtained to evaluate for adrenal rest tumors of the ovaries. Abdominal MRI was obtained to evaluate for residual adrenal tissue. A cystic lesion arising from her right ovary suspicious for ovarian neoplasm was noted on pelvic MRI. Right salpingo-oophorectomy was performed and histopathological examination revealed ovarian serous adenocarcinoma, low-grade, and well-differentiated. Tumor marker CA-125 was elevated and additional ovarian cancer staging workup confirmed stage IIIC due to one lymph node positive for carcinoma. The patient then developed a large left ovarian cyst, which led to a complete total abdominal hysterectomy and removal of the left ovary and fallopian tube. Pathology confirmed ovarian serous adenocarcinoma with microscopic focus of carcinoma in the left ovary. After numerous complications, the patient responded well to chemotherapy, CA-125 levels fell and no evidence of carcinoma was observed on subsequent imaging. To our knowledge, this is the first reported case of an ovarian serous adenocarcinoma in a patient with CAH. Although rare, we propose that the ovaries were the origin of androgen production and not residual adrenal tissue. The relationship between CAH and ovarian carcinomas has yet to be established, but further evaluation is needed given the poor survival rate of high-grade serous ovarian carcinoma.