Tumor heterogeneity is used to define the appearance of different histological differentiation within a single neoplasm. We present a case of single hepatocellular carcinoma showing both low and high FDG uptake areas. The low FDG uptake area was corresponding to low-grade HCC, and the high FDG uptake area was corresponding to high-grade HCC. This case indicates that the tumor grades affect intratumoral heterogeneity in FDG distribution. FDG PET/CT can be useful for guiding tissue sampling of the HCC with heterogeneous histological differentiations, and obviating overestimation or underestimation of the proportion of the higher-risk cell population.