Hepatocellular carcinoma (HCC) incidence rates vary by gender, age, time and place. Geographic differences in gender-, age- and time-specific HCC incidence rates may improve the understanding of HCC risk factors. We computed annual standardized HCC incidence rates for the United States (U.S.) 1978–2004 and for Denmark 1978–2003. Among U.S. white men aged 45–59 the HCC incidence rates were comparable to the Danish rates until 1995, but more than tripled over the following 8 years to become over 2.5-fold higher than the Danish rate by 2003, with an additional small increase in 2004. HCC rates in black U.S. men aged 45–59 also increased sharply after 1995. Among women aged 45–59 the U.S. HCC rates were elevated in recent years, but did not show the sharp increase after 1995 observed among men; the Danish rates showed a decreasing trend throughout 1978–2003. U.S. rates in the 60–74 years age groups showed a protracted and gradual increase with no evidence of a sharp increase after 1995. In the 60–74 years age group, rates for Danish men were comparable to those for U.S. white men, but rates for Danish women decreased. The U.S. prevalence rates of hepatitis C virus (HCV) infection are 2.1 and 1.1% for men and women, respectively, the Danish 0.2%. The disparity in HCV prevalence is the most likely explanation for the differences between Danish and U.S. trends in HCC incidence. Intravenous drug use and blood transfusions are the major sources of HCV, and we suggest that increased HCV infection prevalence among Vietnam era military veterans may contribute to the earlier and steeper HCC incidence increase for U.S. men than for U.S. women. © 2007 Wiley-Liss, Inc.