Objective To assess the role of 18F-FDG PET/CT in initial staging of head and neck squamous cell carcinoma and its impact on changing the management compared to other conventional methods. Patients and methods A prospective study of 31 patients (21 male and 10 female), mean age 49.3 ± 12.1 years with histologically confirmed squamous cell carcinoma of the head and neck (nasopharynx was the commonest cancer in 15 patients (48.4%), poorly differentiated grade represented 64.5% of all tumors. Initial staging was achieved according to routine physical examination, endoscopy, CT, U/S, MRI. Results The overall change in TNM staging by 18F-FDG PET/CT in relation to conventional methods was encountered in 15/31 patients (48.4%). PET/CT changed; T staging in three patients (9.6%), upstaging in two patients and downstaging in one patient. PET/CT upstaged all 13/31 patients in N staging (41.9%). 18F-FDG PET/CT changed; M staging in 3/31 (9.6%) patients, upstaging in two and downstaging in one patient. PET/CT results caused radiotherapy modification in 21/31 patients (67.7%). PET/CT detected intra-parotid nodule in four patients, so additional radiation was added to the parotid in the treatment field. Retropharyngeal nodes were detected by PET/CT in three patients that were missed by conventional imaging. 18F-FDG PET/CT detected two patients of thyroid papillary carcinoma and one case of sigmoid neoplasm confirmed by histopathology. Conclusion 18F-FDG-PET/CT is considered a valuable diagnostic test in head and neck squamous cell carcinoma at initial assessment which would change staging and radiotherapy planning and hence proper management.