The routine use of PET/CT fusion imaging in a large oncology practice has led to the realization that ¹⁸F-FDG uptake into normal fat and muscle can be a common source of potentially misleading false-positive PET imaging in the neck, thorax, and abdomen. The goal of this study was to characterize this normal variant of ¹⁸F-FDG uptake in terms of incidence and characteristic extent. All body scans done on our PET/CT scanners in July and August 2002 were retrospectively reviewed. All cases in which increased ¹⁸F-FDG uptake in the neck was not localized to lymph nodes or other obvious anatomic sites on the CT scans were included in this study. Sites of any unexplained ¹⁸F-FDG uptake in the rest of the body were also recorded. A total of 863 PET scans (476 males, 387 females; age, 2–88 y; mean age, 57 y) were reviewed. The following distinctive patterns of nonpathologic ¹⁸F-FDG activity were observed: (a) neck fat, 20 patients (2.3%); (b) paravertebral uptake, 12 patients (1.4%); (c) perinephric fat, 7 patients (0.8%); (d) mediastinal fat, 8 patients (0.9%); (e) normal musculature, 12 patients (1.4%). Patients showing paravertebral uptake, perinephric fat, and mediastinal fat were all associated with the neck fat pattern, singly or in combination. On the other hand, patients showing the normal musculature pattern did not show any of the other uptake. In this analysis, the incidence of ¹⁸F-FDG uptake in sites other than the neck is restricted to the patient population with neck fat uptake and may be an underestimation of the true incidence. Neck fat is found predominantly in females, whereas normal musculature is usually seen in males (P < 0.01, Fisher exact test). Neck fat is also seen significantly more in the pediatric population (4/26 = 15%) than in the adult population (16/837 = 1.9%) (P < 0.01, Fisher exact test). Increased ¹⁸F-FDG uptake is sometimes seen in individual muscles and in adipose tissue in the neck and shoulder region, axillae, mediastinum, and perinephric regions. There is also associated ¹⁸F-FDG uptake in the intercostal spaces in the paravertebral regions. ¹⁸F-FDG uptake in neck fat is more commonly seen in female patients and the pediatric population. The pattern of uptake as well as the age and sex distribution suggest that the ¹⁸F-FDG in fat is in the brown adipose tissue. It is important to recognize this uptake pattern to avoid false interpretation of this benign normal variant as a malignant finding on ¹⁸F-FDG PET scans.