Fibroblast activation protein-α (FAPα) is an enzyme usually not expressed by normal tissues, but overexpressed stromal fibroblasts typically present in many epithelial cancers, and may potentially represent an attractive target for diagnostic and therapeutic uses. FAPI-based radiopharmaceuticals are a novel class of tracers used in the positron emission tomography (PET) field, which have demonstrated some advantages over [18F]FDG (fluorine deoxyglucose), especially in the case of low-grade or well-differentiated tumors. However, evidence are yet preliminary and not completely understood. We performed this review to investigate the works that performed a head-to-head comparison between FAPI and FDG tracers to evaluate the potential role of FAPI radiopharmaceuticals in the main cancers and in the main settings. FAPI-based radiotracers have demonstrated initial significant findings, especially for the study of, liver and biliary tract, gastrointestinal and breast cancers, and similar performances in head and neck cancer (including also thyroid carcinoma). The superiority of FAPI is described for both the evaluation of primary tumor and distant localizations (nodal and distant metastases). However, further articles with larger samples are mandatory to better clarify all the strengths of these new tracers and the specific diseases where their application could be shareable. This chapter summarizes the main evidence about the clinical potential function of FAPI PET tracers in oncological patients compared to [18F]FDG.