Thyroid incidental uptake is defined as a thyroid uptake incidentally and newly detected by imaging techniques performed for an unrelated purpose and especially for non-thyroid diseases. Aim of the study was to establish the prevalence and pathological nature of focal thyroid incidentalomas detected at F18-FDG-PET/CT in patients studied for oncological purposes and not for thyroid disease. Secondary end point was to establish a possible maximum standardised uptake value cut-off over which a malignant lesion should be suspected. We have retrospectively evaluated 49519 patients who underwent F18-FDG-PET/CT for oncologic purposes in three Nuclear Medicine Centres (N.1 = 11278, N.2 = 31076, N.3 = 7165). A focal incidental thyroid uptake was diagnosed in 729 (1.5 %) patients (287-39.4 % male and 442-60.6 % female; average age: 65.26). Of 729 thyroid incidentalomas 211 (28.9 %) underwent further investigation to determine the nature of the nodule; 124/211 (58.8 %) incidentalomas were benign, 72/211 (34.1 %) malignant, 4/211 (1.9 %) non-diagnostic at cytological examination in the absence of surgery and histological evaluation and 11/211 (5.2 %) were indeterminate at cytological examination. A centre-based receiver operating curve (ROC) analysis of the patients with a definitive diagnosis was performed to identify a SUVmax cut-off useful in differentiating benign from malignant incidentalomas. In the centre N.1 it was 4.8 (sensitivity = 95.7 %, specificity = 46.4 %, area under the curve = 0.758); 5.3 in the centre N.2 (sensitivity = 76.3 %, specificity = 72.5 %, area under the curve = 0.815); 7 in the centre N.3 (sensitivity = 57.1 %, specificity = 79.3 %, area under the curve = 0.627). F18-FDG-PET/CT thyroid incidentalomas are a relevant diagnostic reality which requires further investigations and clinical management especially considering that, despite mainly benign, approximately one third of focal thyroid uptakes are malignant.