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BACKGROUND: The aim of our study was to assess the value of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) for the staging of clinically nodal negative necks in oral and oropharyngeal squamous cell carcinoma (SCC) using sentinel lymph node (SLN) biopsy and elective neck dissection (END) as "gold standard" for comparison. METHODS: Twelve patients (10 men, 2 women) with oral or oropharyngeal squamous cell carcinoma and no evidence of lymph node metastasis in the physical and radiologic examinations were eligible. At least 24 hours before surgery PET with FDG were performed. The SLN was localized by preoperative lymphoscintigraphy with 99m-Tc-Nanocoll and intraoperative use of a hand-held gamma-probe and selectively excised. All patients then underwent END. RESULTS: SLN and END revealed occult metastasis in 5 of 12 cases. SLN biopsy was accurately feasible in all 12 patients and diagnosed all 5 cases of occult metastasis (sensitivity and specificity of 100%). PET suggested two patients having occult metastasis, of which one turned out to be false positive (sensitivity 25%, specificity 88%). The mean size of the micrometastasis was 1.4 mm (range, 1.2-1.5 mm). CONCLUSIONS: PET with FDG turned out to have a poor sensitivity and specificity in revealing occult metastasis and has no role for the evaluation of otherwise clinically N0 necks. The failure to detect micrometastasis by PET is due to the technical limitations of resolution (4-5 mm). SLN biopsy, with END in cases of positive SLN, provides a highly accurate staging of N0 necks in oral and oropharyngeal carcinoma. Patients with negative SLN could be spared the risks and the morbidity of END.