This article reviewed comparative studies of the use of F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) and sentinel lymph node biopsy (SLNB) for the detection of regional lymph node metastasis in patients with various malignancies. We sought to evaluate the diagnostic accuracy of F-FDG PET (PET/CT) compared with SLNB to determine the presence or absence of regional lymph node metastasis. In this paper, we review 15 comparative studies of breast tumors and 17 comparative studies of melanomas that used these methods to detect regional lymph node metastasis. Original articles for other malignancies, including oral and oropharyngeal carcinoma, penile carcinoma, anal cancer, and cervical cancer, are relatively scarce. A consensus has been reached in the literature that SLNB is much more sensitive than F-FDG PET and PET/CT for detecting small lymph node metastasis. F-FDG PET and PET/CT cannot replace SLNB for the evaluation of early-stage regional lymphatic tumor dissemination in this patient population.