The appropriate use criteria (AUC) documents are intended to aid medical practitioners in the appropriate use of imaging technology in specific clinical scenarios based on rigorous appraisal of the available published evidence. The purpose of this document is to summarize the appropriate use of PET/CT with ¹⁸F-FDG in the initial staging of malignant disease. A multidisciplinary expert panel convened to appraise an independently performed systematic review and develop the AUC for initial staging of head and neck cancer, lung cancer, breast cancer, esophageal cancer, colorectal cancer, pancreatic cancer, melanoma, lymphoma, myeloma, and sarcoma with an appropriateness score for each clinical scenario established by using a modified Delphi process (Table 1). The full document including the methodology details, discussion of evidence, appendices, and the supplemental material can be accessed at https://snmmi.org/Web/Clinical-Practice/Appropriate-Use-Criteria/Articles/Appropriate_Use_Criteria_for_18F-FDG_PET_CT_for_Initial_Staging_of_Malignant_Disease.