A 56-year-old man was diagnosed with cancer of the ascending colon along with retroperitoneal lymph node and peritoneal metastases. After six cycles of palliative chemotherapy, he presented with acute-onset jaundice. Imaging examinations did not show abnormal liver findings other than a periportal linear hypoattenuating area, and endoscopic retrograde cholangiography revealed a tight stricture of the proximal common bile duct. Total bilirubin continued to increase after endoscopic sphincterotomy and biliary stent insertion. Blind liver biopsy revealed tumor infiltration along liver lymphatics, but ruled out tumor involvement of hepatic parenchyma and sinusoids. Tumor cells were predominantly confined to within the lymphatic vessels and were not observed in the arteries or veins. Although one loading dose of cetuximab and two fractions of palliative radiotherapy were administered, the patient succumbed to acute liver injury 30 days after the development of jaundice.