Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) is an uncommon form of primary liver cancer with features of hepatocellular and biliary epithelial differentiation. The clinical significance of this disease entity is poorly understood. The aim of the present study was to determine the operative and survival outcomes of patients with HCC-CC who underwent hepatic resection. Retrospective study. Tertiary referral center. The study comprised 12 patients (aged 28-72 years) with HCC-CC (HCC-CC group) who underwent hepatic resection between January 1, 1991, and December 31, 2000. The diagnosis was based on a combination of histological, immunohistochemical, and, if necessary, electron microscopic examinations of the resected specimen. Clinicopathological data and operative and survival outcomes of the HCC-CC group were compared with those of 476 patients with HCC (HCC group) and 25 patients with intrahepatic CC (CC group) who underwent hepatic resection during the study period. Ten patients (83%) in the HCC-CC group underwent major hepatic resection. The operative morbidity and mortality were 17% (2 of 12 patients) and 0%, respectively. The clinicopathological variables of the HCC-CC group resembled those of the HCC group more closely than those of the CC group. The incidence of positive hepatitis B serologic test results in the HCC-CC group (7 [58%] of 12 patients) was intermediate between that of the HCC group (392 [82%] of 476 patients) and that of the CC group (5 [20%] of 25 patients) (P<.001). Underlying chronic liver disease was significantly less common in the CC group (5 [20%] of 25 patients) than in either the HCC-CC group (9 [75%] of 12 patients) or the HCC group (421 [88%] of 476 patients) (P<.001). After hepatic resection, the median disease-free survival of the HCC-CC, HCC, and CC groups was 10, 18, and 24 months, respectively (P =.44). The overall median survival was shortest in the HCC-CC group (17 months) and was not significantly different from that of the CC group (26 months) (P =.38), but was significantly worse than that of the HCC group (52 months) (P =.02). Although the clinicopathological variables of patients with HCC-CC were most similar to those of patients with HCC, patients with HCC-CC had a significantly worse survival outcome after hepatic resection when compared with patients with HCC. Further studies on postoperative adjuvant therapy and multimodality treatment for recurrent disease are required to prolong the survival of these patients.