Although the term mixed metabolic response is commonly used in PET/CT reports, it should be a red flag to reconsider the assumptions made by the PET scan reader. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT is recognized as an accurate imaging method for detecting response to cancer therapies. Critical clinical decisions regarding therapy are dependent on accurate interpretation of findings. The use of standardized terminology for response assessment, such as that in the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), is highly recommended. With PERCIST, treatment response is categorized as complete metabolic response, partial metabolic response, stable metabolic disease, or progressive metabolic disease. Mixed metabolic response is not included in PERCIST. Rather, it is used colloquially to describe a scenario in which scanning performed after systemic cancer therapy reveals divergent findings, with some tumor foci responding and others not responding or even seen progressing. In PERCIST, mixed metabolic response should be described as stable metabolic disease or progressive metabolic disease. However, the PET/CT reader may also wish to suggest that individual tumors have heterogeneous genetic and/or other characteristics and consequently a mixed response to therapy. The concept of tumor heterogeneity is gaining momentum in cancer research and thus possibly leading to options for therapy targeted to oligometastases that are not responding. However, the authors suggest exercising extreme caution when PET/CT findings appear at first to reflect what some might call a mixed response. In addition, they have found that FDG PET/CT findings are often confounding owing to the simultaneous presence of two or more unrelated disease processes. Common examples include synchronous neoplasms, inflammatory processes, and treatment-related effects. Thus, an apparent mixed response is a red flag to reconsider whether all of the FDG-avid findings are actually metastases of the same cancer. Common mimics of a mixed metabolic response that do not represent true tumor heterogeneity are highlighted to improve the FDG PET/CT reader's recognition of these lesions.©RSNA, 2019.