The following report describes a ten-year-old spayed-female Maltese dog, who presented to Cornell University Hospital for Animals for evaluation of hepatobiliary disease. The patient had a six-month history of progressive disease involving vomiting, hyporexia, icterus, and ascites. Hepatobiliary values remained elevated despite treatment with antimicrobials and hepatoprotectants. Diagnostics performed at Cornell included a complete blood count, serum chemistry panel, urinalysis, disseminated intravascular coagulation panel, protein C, and abdominal ultrasound. Bloodwork confirmed persistent elevations in hepatobiliary values and disclosed low protein C, suggesting portosystemic shunting. Abdominal ultrasonography revealed signs consistent with portal hypertension, including free peritoneal fluid, multiple acquired portosystemic shunts, and hepatofugal blood flow in the portal and splenic veins. Echocardiography and ultrasonography ruled out pre- and post-hepatic causes of portal hypertension. An exploratory laparotomy was performed and biopsies of the liver and small intestines were collected. Histopathologic evaluation revealed multiple causes of intrahepatic portal hypertension, including: parenchymal collapse, veno-occlusive disease, and chronic cholangiohepatitis. Post-operatively, the patient experienced severe acute anemia secondary to gastrointestinal hemorrhage, which was likely due to rupture of acquired portosystemic shunt vessels. Transfusions of packed red blood cells and fresh frozen plasma were administered and the patient stabilized. She was discharged one week post-admission with broad-spectrum antibiotics, diuretics, hepatoprotectants, gastroprotectants, and an analgesic. The patient passed away five weeks after discharge.