Hepatocellular carcinoma may seem to be a natural candidate for screening. In high-risk groups in the United States, the risk for HCC may range from 10% to 65% (3) over 10 years; HCC incidence and mortality are increasing among Vietnam-era veterans and others among whom hepatitis C is prevalent; and 5-year survival with HCC in the absence of screening is dismal (<10%). Ultrasonography can detect HCC at an early preclinical stage and can increase the proportion of patients who receive potentially curative therapy (resection or transplant). All of this, however, is necessary but not sufficient to support cancer screening. As noted by Kansagara and colleagues, the evidence that screening reduces cancer mortality has major limitations. One randomized screening trial in China among patients with chronic hepatitis B showed a significant mortality benefit (hazard ratio, 0.63) but had many methodological flaws; a smaller, better-designed Chinese trial showed no benefit but may have employed an insufficiently sensitive screening protocol (4). A study examining different screening intervals showed that improving early detection does not necessarily improve survival. Moreover, because hepatitis B virus is associated with HCC in the absence of cirrhosis, it is not clear whether these studies can be generalized to at-risk patients in the United States, most of whom have cirrhosis due to chronic hepatitis C or alcohol use.