INTRODUCTION: Beta-hCG-secreting choriocarcinomas are rare, rapidly-growing, highly-invasive malignant tumors that present most often in the uterus after pregnancy or abortion, as it is a remnant from trophoblastic or totipotent germ cells. Primary extragonadal choriocarcinomas of the GI tract are very rare, with the majority within or along with adenocarcinomas of the organ in question. CASE DESCRIPTION/METHODS: A 29-year-old woman presented with 2.5 weeks of jaundice of the skin. The patient had severe microcytic anemia (Hb 6.8 g/dL), elevated liver enzymes (AST 77 U/L, ALT 95 U/L, Alk Phos 362 U/L), total bilirubin (9.5 mg/dL; 4.4 mg/dL direct), lipase (325 U/L), and CA19-9 (68 U/mL). Pregnancy tests revealed elevated serum and urine beta-hCG. Subsequent ultrasound showed no intrauterine pregnancy. CT of the abdomen with IV contrast revealed a large (7.5 × 5.0 × 7.0 cm), non-obstructing, lobulated mass in the second and third part of the duodenum, displacing the head of the pancreas (Figure 1). An adjacent lesion to the left of the dominant mass measured 3.5 × 2.5 cm, with two regional lymph nodes in the adjacent bowel mesentery. Both pancreatic duct dilation (6 mm) and CBD dilation (15 mm), with accompanying intrahepatic duct dilation, are shown (Figure 1). Endoscopy with biopsies revealed an invasive, well-differentiated adenocarcinoma, with cytoplasmic-stained cells with antibody to beta-hCG antigen, suggesting a choriocarcinoma (Figures 2–3). Treatment included biliary drainage with a percutaneous transhepatic catheter and FOLFOX chemotherapy. A CT scan five months later revealed an increase in duodenal tumor size with invasion into the pancreas and right hepatic lobe. Palliative radiotherapy was initiated, but the patient died several months later. DISCUSSION: We present the case of a never-pregnant female with jaundice found to have a lobular duodenal adenocarcimoa with histology positive for a rare beta-hCG-secreting duodenal choriocarcinoma. One choriocarcinoma theory suggests that remnant totipotent stem cells recently differentiated into neoplastic beta-hCG-secreting cells. Another choriocarcinoma theory, called the dedifferentiation theory, states that malignant adenocarcinoma cells dedifferentiated to ectodermal cells then re-differentiated to beta-hCG-secreting trophoblastic cells. Patients may present with anemia or bleeding from the ulcerated mass, mimicking peptic ulcer disease. Our patient’s advanced duodenal tumor caused biliary obstruction-induced jaundice as initial presentation.Figure 1.: The large 7.5 × 5.0 × 7.0 cm lobulated, non-obstructing, duodenal mass is seen displacing the head of the pancreas superiorly and anteriorly. An adjacent satellite lesion to the left of the dominant mass measures 3.5 × 2.5 cm, with two regional lymph nodes in the adjacent bowel mesentery. The dominant mass abuts the inferior vena cava and aorta. Both pancreatic duct dilation (6 mm at site of pancreatic head) and common bile duct dilation (15 mm), with accompanying intrahepatic duct dilation, are shown.Figure 2.: Cytoplasmic-stained cells with antibody to beta-hCG antigen, suggesting a choriocarcinoma. Tumor sequencing found 14 genomic mutations, including KRAS and TP53.Figure 3.: Cytoplasmic-stained cells with antibody to beta-hCG antigen, suggesting a choriocarcinoma. Tumor sequencing found 14 genomic mutations, including KRAS and TP53.