(18)F-Fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) is increasingly being used for the evaluation of several malignancies. Key to the correct interpretation of oncological FDG-PET studies is awareness of the concept that the degree of FDG uptake reflects the biology of the tumor in many cancers. More specifically, cancers with high FDG uptake are often histologically and clinically more aggressive than those with low or no FDG uptake. Therefore, although a negative FDG-PET scan in a patient with a cancer that has a size above the spatial resolution of PET may be interpreted as false-negative in terms of tumor detectability, it should in fact be regarded as true-negative from the view-point of tumor biology. This nonsystematic review will give examples of several major cancers in which the relationship between FDG avidity and tumor biology is applicable, and emphasizes the need to reconsider the definition of a "false-negative" FDG-PET scan in clinical oncology.