¹⁸F-FDG PET/CT was used for evaluation of spleen infiltration in patients with B-cell non-Hodgkin lymphoma (NHL). Five patients with histological diagnosed B-cell NHL underwent ¹⁸F-FDG PET/CT examination. On integrated PET/CT image, spleen infiltration was considered when PET images revealed a discrete margin of solid splenic masses or diffuse lesion of spleen with higher maximum standardized uptake value (SUV) greater than those of normal liver structures. CT images demonstrating a positive splenic index (>480 mL) or focal hypodensities were classified as positive for spleen infiltration. All the patients underwent systemic chemotherapy. The ¹⁸F-FDG PET and CT results were compared with final diagnoses. All patients had spleen infiltration originating from B-cell NHL at final diagnosis. Final diagnoses, which were confirmed by clinical and CT (n=3) or ¹⁸F-FDG PET/CT (n=1) follow-up in 4 patients and biopsy of 1 patient. On integrated PET/CT image, ¹⁸F-FDG PET was true-positive in all 5 patients with spleen infiltration. CT was true-positive in 4 of the 5 patients with spleen infiltration and false-negative in 1 patients (spleen infiltration without morphology changes). The accuracies of ¹⁸F-FDG PET and CT for evaluating the spleen infiltration were 100% and 80% at staging, respectively. Our preliminary results suggested metabolic imaging of ¹⁸F-FDG PET/CT may be helpful in the diagnosis of spleen infiltration in B-cell NHL patients. These patients may benefit from ¹⁸F-FDG PET/CT in diagnosis, when spleen infiltration without morphology changes, which may not be diagnosed exactly by conventional image.