Measurement of serum AFP can be useful in the diagnosis of hepatocellular carcinoma (HCC). AFP is a fetal protein that is not normally present in the serum of adults but is elevated in most patients with HCC. The diagnosis of HCC is generally made in patients with a mass lesion in a cirrhotic liver if the AFP is over 400 ng/ml. Unfortunately, AFP is elevated in other conditions such as nonseminomatous germ cell tumor, chronic hepatitis, cirrhosis, pregnancy, and hepatic metastasis. A high AFP cutoff value for HCC would increase the specificity of the test, but would decrease the sensitivity considerably. We report the case of a patient with HCV and cirrhosis with a markedly elevated AFP of 1257 ng/ml in whom no evidence of HCC could be found after a thorough radiologic and histologic evaluation. Despite a virologic nonresponse to IFN-alpha2b and ribavirin therapy, there was a complete normalization of AFP.