Abstract Obesity confers an increased incidence and poorer clinical prognosis in more than 10 cancer types. Paradoxically, obesity may provide protection from poor outcomes in lung cancer. Mechanisms for the obesity-cancer links are not fully elucidated, with altered glucose metabolism being a promising candidate. Using 18F-fluorodeoxyglucose positron-emission-tomography/computed tomography images from The Cancer Imaging Archive, we explored the relationship between body mass index (BMI) and glucose metabolism in several cancers. In 188 patients (BMI mean [SD] = 27.7 [5.1], range = 17.4–49.3 kg/m2), higher BMI was associated with greater tumor glucose uptake in breast cancer (r = 0.36; P = .02) and with lower tumor glucose uptake in non-small cell lung cancer (r = -0.26; P = .048) using two-sided Pearson correlations. No relationship was observed in soft tissue sarcoma or squamous cell carcinoma. Harnessing the National Cancer Institute’s open-access database, we demonstrate altered tumor glucose metabolism as a potential mechanism for the detrimental and protective effects of obesity on breast and lung cancer, respectively.