BackgroundLymphoma is found to be the main source of non-infectious fever of unknown origin (FUO). However, there is a lack of clinical features and outcomes in lymphoma patients initially presenting as FUO.MethodsFrom January 1, 2013 to December 31, 2019, our center enrolled 185 patients who initially presented as FUO then confirmed to be lymphoma in Huadong Hospital of Fudan University. During the same study period, 332 lymphoma patients without FUO received treatment in our center. After the exclusion, 509 patients were included in the retrospectively study. The differences in clinical manifestations, laboratory examinations, overall response rates and survival rates between the FUO and non-FUO groups were analyzed. The clinical endpoints were overall survival (OS) and progress-free survival (PFS).ResultsIn the non-FUO group (329 in total), Hodgkin’s lymphoma (HL) was 17 (5.2%), B cell non-Hodgkin’s lymphoma (B-NHL) was 276 (83.9%), T cell non-Hodgkin’s lymphoma (T-NHL) was 32 (9.7%) and NK/T cell lymphoma (NK/T-CL) was 4 (1.2%). In the FUO group (180 in total), B-NHL was 88 (48.9%), T-NHL was 60 (33.3%), NK/T-CL was 24 (13.3%) and HL was 8 (4.4%). During the hospitalization, the maximum body temperature of the FUO group diagnosed with B-NHL, T-NHL and NK/T-CL was statistically higher than that of the non-FUO group (all P<0.05). Concerning the overall response rates, there was no difference between the FUO and non-FUO groups, whatever the pathological subtype was. The differences in OS between the FUO and non-FUO groups were significant for HL (P=0.006), B-NHL (P=0.007) and T-NHL (P=0.013). No difference in overall survival was observed in the two groups for the subtype of NK/T-CL (P=0.141). In terms of PFS, there was no significant difference between FUO and non-FUO groups for any subtype (all P>0.05).ConclusionWe found that the major subtypes of lymphoma initially presenting as FUO were B-NHL and T-NHL. The main diagnostic biopsy sites were subcutaneous lymphnodes, bone marrow and spleen for lymphoma patients with FUO. Patients with FUO suffered from a higher risk of all-cause death in the long term.