OBJECTIVE: FDG-PET/CT (fluorodeoxyglucose-positron emission tomography/computed tomography) is effective to assess for occult neck nodal disease. We report risks and patterns of nodal disease based on primary site and nodal level from data on the dissected cN0 per the results from ACRIN 6685. STUDY DESIGN: Prospective nonrandomized enrollment included participants with first-time head and neck squamous cell carcinoma and at least 1 cN0 neck side to be dissected. SETTING: Twenty-four ACRIN-certified centers internationally (American College of Radiology Imaging Network). METHODS: A total of 287 participants were enrolled. Preoperative FDG-PET/CT findings were centrally reviewed and compared with pathology. Incidence, relative risk, pattern of lymph node involvement, and impact upon neck dissection were reported. RESULTS: An overall 983 nodal levels were dissected (n = 261 necks, n = 203 participants). The highest percentages of ipsilateral positive nodes by primary location and nodal level were oral cavity (level I, 17/110, 15.5%), pharynx (level II, 6/30, 20.0%), and larynx (level VI, 1/3, 33.3%). CONCLUSION: Levels at greatest risk for nodal disease in cN0 in terms of ipsilateral neck dissection are level I (oral cavity), II (pharynx), and VI (larynx). These data should be considered when treating patients presenting with cN0. This is the first study to comprehensively report the incidence, location, and risk of metastases in cN0 in the FDG-PET/CT era.