Purpose <p>Accurate initial staging of differentiated thyroid carcinoma (DTC) is paramount to avoid disease persistence or relapses. Neck ultrasound (US) is the gold-standard examination for lymph node staging; however, it might miss the central compartment ones. [¹⁸F]FDG PET/CT has been used to characterise unclear or suspicious thyroid nodules and can also identify nodal disease. This study tested the diagnostic efficacy of a combined approach, including digital [¹⁸F]FDG PET/CT of the cervical region and neck US in DTC staging.</p> Methods <p>We retrospectively evaluated consecutive patients treated at our centre with high-risk thyroid who had had a neck US and a neck digital [¹⁸F]FDG PET/CT before surgery and at least one year of follow-up. Diagnostic parameters, including sensitivity (Se) and accuracy (Acc), were compared across US alone, [¹⁸F]FDG PET/CT alone, and the combined approach using a patient-based analysis (PBA); Se was also tested employing a lesion analysis (LBA). Clinical and SUV parameters were compared with the histology and the one-year outcome via a logistic regression model.</p> Results <p>Eighty-two patients (61 females) were included. At the PBA, the combined approach was superior to US alone regarding Se (44% vs 19%, <i>p</i> &lt; 0.05) and Acc (80% vs 72%, <i>p</i> &lt; 0.05) in the central compartment nodes. At the LBA, the combined approach was superior to either method overall (43%, 37%, and 36% for combined, [¹⁸F]FDG, and US, respectively, <i>p</i> &lt; 0.01) and to US in the central nodes (25% vs 14%, <i>p</i> &lt; 0.01). SUVratio was an independent predictor of histologically aggressive DTC variants (<i>p</i> = 0.009), central compartment metastases (<i>p</i> = 0.04), and incomplete response at follow-up (<i>p</i> = 0.004).</p> Conclusions <p>The combined cervical [¹⁸F]FDG PET/CT / US approach improves the initial staging and harbours valuable prognostic information for DTC patients.</p>