This review focuses on the use of 18F-FDG PET/CT to evaluate second primary cancers. The emergence of a second primary cancer is an important prognostic factor in cancer patients. The early detection of a second primary cancer and the appropriate treatment are essential for reducing the morbidity and mortality associated with these tumors. Integrated 18F-FDG PET/CT, which can provide both the metabolic and anatomic information of a cancer, has been shown to have a better accuracy in oncology than either CT or conventional PET. The whole body coverage and high sensitivity of 18F-FDG PET/CT along with its ability to provide both metabolic and anatomic information of a cancer make it suitable for evaluating a second primary cancer in oncology. Whole body 18F-FDG PET/CT is useful for screening second primary cancers with a high sensitivity and good positive predictive value. In order to rule out the presence of a second primary cancer or an unexpected metastasis, further diagnostic work-up is essential when abnormal findings indicative of a second primary cancer are found on the PET/CT images. PET/CT is better in detecting a second primary tumor than conventional PET.