Advanced hepatocellular carcinoma is characterized by a poor prognosis, and the choice of therapy is complicated in cases with cardiac metastasis due to the questionable benefits of surgery. Since many studies have indicated that mucin (MUC) expression plays an important role in cancer metastasis and recurrence, we investigated mucin expression in hepatocellular carcinoma patients with cardiac metastasis compared with primary hepatocellular carcinoma to confirm the nature of the malignancy. Over a 6-year period, the expression patterns of MUC1, MUC2 and MUC5AC in tumor samples from hepatocellular carcinoma patients with cardiac metastasis were assessed using immunochemistry. The results were compared with findings from a group characterized by a more favorable prognosis; those with primary hepatocellular carcinoma without recurrence. Pathologic examinations indicated that patients with hepatocellular carcinoma and cardiac metastasis had more vascular invasion (P=0.004) and less section-free zone involvement (P<0.001) than those with primary hepatocellular carcinoma. MUC1 expression was significantly higher in hepatocellular carcinoma with cardiac metastasis (P<0.005). In conclusion, the expression of mucins, especially MUC1, confirms the malignant nature of hepatocellular carcinoma with cardiac metastasis. It is recommended that such patients receive aggressive therapy.