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Objective: The purpose of this study was to determine the sensitivity and specificity of (18)F-FDG PET, CT, and combined PET/CT in the detection of splenic involvement at initial staging of lymphoma., Materials and Methods: A retrospective longitudinal analysis was performed on the records of 111 patients with proven lymphoma who had undergone PET and CT before and after treatment. CT scans were evaluated independently by two radiologists, and PET scans by two nuclear medicine physicians. Abnormal CT findings were defined as low-attenuation nodules or a splenic index greater than 725 cm(3) (> 2 SDs above the mean in 100 controls). An abnormal PET finding was defined as splenic uptake greater than hepatic uptake. True splenic involvement was defined retrospectively on the basis of the treatment response assessed with criteria revised in the International Harmonization Project on lymphoma. Observer agreement and sensitivity and specificity values were calculated., Results: Observer agreement for CT splenic index and PET findings was good. For initial splenic staging, the sensitivity and specificity of CT, PET, and PET/CT were 91% and 96%, 75% and 99%, and 100% and 95%., Conclusion: For initial staging of splenic involvement in malignant lymphoma, the sensitivity and specificity of PET/CT can reach 100% and 95%. The sensitivity of the combined approach is higher than that of either technique alone.