Alpha-fetoprotein (AFP)-L3 was originally reported as a hepatocellular carcinoma (HCC)-specific tumor marker, and recent accumulation of evidence has revealed that AFP-L3 frequency predicts the biological malignancy potential of HCC. However, AFP-L3 elevation from undetectable levels after curative treatment could not be discussed due to the difficulties of calculating AFP-L3 concentrations when serum AFP levels were low. Here, as a novel method, we used highly sensitive AFP-L3 frequency to predict HCC recurrence after curative treatment. Our cases illustrate that recognizing elevation of AFP-L3 from undetectable levels led to the early detection of recurrent HCC due to more careful surveillance.