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A 71-year-old woman with abnormal liver function was referred to another hospital. During follow-up, she developed refractory leg edema and ascites and was subsequently referred to our institute. Despite multiple imaging studies, including dynamic computed tomography (CT), Gd-EOB-DTPA magnetic resonance imaging (MRI), angiographic CT, and perflubutane-enhanced ultrasound, a definitive diagnosis could not be established. Liver biopsies from three sites with different imaging findings revealed adenocarcinoma of bile duct origin, and the patient was diagnosed with unresectable intrahepatic cholangiocarcinoma involving nearly the entire liver. She received gemcitabine/cisplatin, but treatment was discontinued early due to severe anorexia. Palliative care was provided, but she died approximately six months after diagnosis. This case highlights the diagnostic difficulty of imaging alone and underscores the value of liver biopsy when imaging findings are inconclusive.