Background The aim of this study is to evaluate the diagnostic performance of contrast-enhanced computed tomography (CECT) and 2-[Fluorine-18] fluoro-2-deoxy-d-glucose positron emission tomography combined to computed tomography (18 F-FDG PET/CT) in assessment of lymphoma. Methods Hundred patients, pathologically proven as lymphoma, were evaluated by CECT and 18F-FDG PET/CT for initial assessment and staging of the disease. The number of lesions and the disease stage detected by each modality was calculated and further analyzed to be compared. Results 18F-FDG PET/CT diagnosed a total number of 545 lymphoma involved regions with sensitivity 96.6%, specificity 98.8%, and accuracy 99% that was higher than CECT which diagnosed a total number of 439 lymphomatous regions with sensitivity 87.5%, specificity 85.7%, and accuracy 88%. Discordant staging by both modalities was found in 23% of the patients. Lymphoma was upstaged by PET/CT in 17% of the patients; with major changes in 12% of them and downstaged in 6% of the patients. Conclusion 18F-FDG PET/CT scan has a better diagnostic performance, represented by sensitivity, specificity, and accuracy, than CECT scan in the initial assessment of lymphoma regarding its nodal and extra-nodal lesions that could lead to alteration of disease staging which in turn markedly affecting the decision of treatment regimens.