Solitary extramedullary plasmacitomas (SEMP) of the liver are very rare. We report the case of an elderly woman with a huge symptomatic SEMP of the liver mimicking hepatocellular carcinoma (HCC). The patient was a 89-year-old woman who presented with severe abdominal pain and a huge solid mass in the right hypochondrium. The laboratory data on admission revealed normal liver function tests. A multiphasic computed tomography (CT) showed a huge solid mass of the left hemiliver, hypoattenuating on noncontrast images, dishomogeneously hyperenhancing in the late arterial phase, with washout in the portal venous and equilibrium phases. A 18F-FDG positron emission tomography (18F-FDG PET)-CT scan documented a marked FDG uptake within the lesion, without evidence of extrahepatic metastases. We considered the clinical and radiologic findings consistent with the diagnosis of high-grade HCC with areas of intratumoral necrosis preluding to possible tumour rupture. Surgical resection was ultimately considered feasible with a reasonable risk and the patient underwent left hepatectomy with diaphragmatic resection. Pathological examination exhibited an extramedullary plasmacytoma. At immunohistochemical analysis neoplastic cells were positive for CD45, CD38, IRF4, HTPD52, kappa-chain, but negative for lambda-chain; Mib-1 proliferation index was 50%. Subsequent clinical evaluation excluded any sign of multiple myeloma, so that a diagnosis of truly localized SEMP of the liver was finally established. To our knowledge, this is the first case of a solitary extramedullary plasmacitoma of the liver undergoing successful radical liver resection. The patient is alive and well 5 years after surgery without evidence of local recurrence and of systemic disease.