The aim of the study was to compare differences between lymphoma and inflammation as indicated by high diffuse uptake of F-fluorodeoxyglucose (F-FDG) in the spleen, liver, and bone marrow without increased F-FDG uptake in the lymph nodes and without enlarged peripheral lymph nodes.Eighteen lymphoma patients and 14 inflammation patients were examined with F-FDG positron emission tomography-computer tomography (PET-CT). All patients displayed high diffuse uptake of F-FDG in the spleen, liver, and bone marrow without increased F-FDG uptake in the lymph nodes and without enlarged peripheral lymph nodes. Our analyses compared the maximum standardized uptake values (SUVmax) of F-FDG uptake ratios between the spleen/liver, the spleen/bone marrow, and the liver/bone marrow and further compared spleen sizes between lymphoma and inflammation patients.Using Student t test, no significant differences were found in the SUVmax ratios of spleen/liver and liver/bone marrow between the lymphoma and inflammation patients (t = 0.853, P = 0.401 > 0.05; t = 1.622, P = 0.115 > 0.05). However, the SUVmax ratio of the spleen/bone marrow of the lymphoma patients was significantly different from that of the inflammation patients (t = 2.426, P = 0.021 < 0.05). The spleen size between the lymphoma and inflammation patients was also significantly different (t = 2.911, P = 0.007 < 0.05).As indicated by F-FDG PET-CT, our study demonstrated that lymphoma and inflammation patients displayed a few differences despite both having high diffuse uptake of F-FDG in the spleen, liver, and bone marrow without enlarged peripheral lymph nodes and without increased F-FDG uptake in lymph nodes.