Patient: Female, 28-year-old Final Diagnosis: Hepatic metastasis • metastatic breast cancer • sinusoidal occlusive syndrome Symptoms: Abdominal distension • abdominal pain • lower extremity edema • nausea • vomiting Medication:— Clinical Procedure: — Specialty: General and Internal Medicine • Oncology Objective: Challenging differential diagnosis Background: Hepatic metastasis is well known in breast cancer. Approximately 12–20% of breast cancer patients will develop liver metastasis, which usually presents as discrete mass lesions. Rarely, metastatic spread can be so diffuse that it is unidentifiable on imaging but can progress to fulminant hepatic failure. Our case report suggests that clinicians need to have a high index of suspicion when patients present with rapidly decompensating liver failure in the absence of discrete radiologic hepatic lesions, and that weekly Adriamycin should be considered as a first-line therapeutic option. Case Report: A 28-year-old African American woman with a history of locally advanced estrogen receptor-positive, progesterone receptor-negative, and HER2-negative breast cancer presented with right upper quadrant abdominal pain and bilateral lower extremity swelling. She had been treated 3 years prior with neoadjuvant Adriamycin/cyclophosphamide – Taxol, bilateral mastectomies, radiation therapy, and tamoxifen. Diagnostic imaging revealed massive hepatomegaly and extensive areas of liver ischemia/necrosis without discrete masses or arterial/venous thrombosis. Biopsy of the liver revealed metastatic carcinoma diffusely infiltrating the hepatic sinusoids. Extensive work up for other etiologies of liver disease was negative. The patient’s liver function quickly decompensated over several days. She was treated with weekly single-agent low-dose Adriamycin, and this resulted in successful reversal of her liver function tests back to baseline. Conclusions: In addition to having a high index of suspicion for diffuse intrasinusoidal hepatic metastasis, physicians should consider weekly low-dose Adriamycin as a first-line therapeutic option for patients with progressive liver failure and biopsy-confirmed metastatic carcinoma diffusely infiltrating the hepatic sinusoids.