Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc. Rationale: It is often challenging to discriminate between intrahepatic cholangiocarcinoma (ICC) and metastatic liver tumors, especially when the hepatic tumor is small and of a mass-forming type. Patient concerns: We report a 69-year-old woman presented at our hospital with a small solid tumor in the head of the pancreas that was previously discovered during a medical checkup. Diagnoses: The patient was diagnosed with synchronous pancreatic cancer and ICC. Interventions: The patient underwent clinical, histological, immunohistological, and KRAS mutational analysis. Outcomes: Computed tomography revealed poorly enhanced small nodules in both the pancreatic head and liver. Biopsies of both nodules revealed adenocarcinoma; however, it was unclear whether the hepatic lesion was a metastasis of the pancreatic tumor or primary ICC. KRAS mutational analysis from FFPE biopsy samples revealed a discordance of mutation status between the tumors. Therefore, the patient was diagnosed with synchronous pancreatic cancer and ICC, whereupon she underwent hepatopancreatoduodenectomy. Lessons: KRAS mutational analysis of FFPE biopsy samples can be utilized for differentiating between ICC and metastatic liver tumor.