In patients with a neck metastasis from an unknown primary with non-squamous cell cancer (non-SCC) histology, the primary is often located outside the head and neck area. We retrospectively evaluated 326 patient records and found 14 patients with non-SCC neck lymph node metastasis from an unknown primary undergoing whole body F-18-Xuorodeoxyglucose (FDG) positron emission tomography (PET) with or without coregistered computed tomography (PET/ CT). The PET or PET/CT Wndings were veriWed by pathological work-up, additional imaging tests, and clinical follow-up. PET detected pathological FDG uptake suspicious for the primary in eight patients. PET or PET/CT Wndings were true positive in seven patients, true negative in 4, false positive in 1, and false negative in two patients. In one patient PET/CT revealed a synchronous ovarian carcinoma. The results suggest that whole body imaging with FDG PET and PET/CT can be useful to identify unknown primaries of non-SCC origin. However, the work-up of patients undergoing PET or PET/CT in our study was very heterogeneous and the primary was more likely found in patients without extensive imaging before PET scanning. Further studies should evaluate if the histology of a neck nodal metastasis should inXuence the choice of the imaging method and the role of PET and PET/CT imaging for the work up of patients with a non-SCC neck lymph node metastasis of an unknown primary.