In a consecutive series of 393 patients with excised and pathologically proven primary liver cancer (PLC)--including 374 hepatocellular carcinomas (HCC), nine cholangiocellular carcinomas (CCC), and ten mixed type of HCC and CCC--33 patients (8.4%) had one or two other malignancies in the extrahepatic organ(s). Of these, 29 had double cancers and four, triple cancers. This was synchronous in 11 patients, metachronous in 20 (including 18 with double cancers and two with triple cancers) and synchronous and metachronous in two with triple cancers. Metachronous cancer was found in 21 patients 1 year before hepatectomy for PLC and in three patients, 1 year after hepatectomy. The median age of PLC patients with multiple primary cancer (MPC) was 63.6 +/- 6.9 years; this was significantly greater than that of PLC patients without MPC (P less than 0.01). The associated cancer was gastric cancer in 11 patients (29.7%), colorectal cancer in six, pharyngeal cancer in four, and other cancers in ten different organs in 16. Thirteen of 22 patients had a history of blood transfusion. The incidence of liver cirrhosis in PLC associated with MPC (57.6%) was significantly lower than that without MPC (82.8%, P less than 0.01). The differential diagnosis of PLC from liver metastasis was possible retrospectively in 78.6% using sonograms, 79.3% using computed tomograms, and 91.3% using angiograms. The survival rates of patients with PLC with (n = 33) and without (n = 299) MPC who had undergone hepatectomy were 97.0% and 85.4% at 1 year, 55.5% and 59.5% at 3 years, and 40.5% and 40.1% at 5 years, respectively. There was no significant difference between the survival rates of those who underwent operations for PLC and extrahepatic primary cancer(s) synchronously and metachronously.