Rosai-Dorfman disease (RDD) is a rare macrophage-related histiocytic disorder that occurs primarily in lymph nodes or extranodal sites. Primary splenic lymphoma is an even rarer form of malignant lymphoma exhibiting characteristic diagnosis, treatment and outcome that have been poorly documented. Documentation of a rare case of primary splenic diffuse large B-cell lymphoma concomitant with isolated thymus RDD is reported in a 42-year-old male patient who was admitted to our hospital for persistent fever and splenomegaly after diagnostic thymectomy. On pathological review of the patient's resected thymus tissue, notable characteristics of thymus RDD were observed. The patient's condition quickly deteriorated, and the spleen progressively enlarged over the course of steroid treatment in our facility. Subsequent diagnostic splenectomy results indicated that non-Hodgkin's lymphoma (nongerminal center diffuse large B-cell lymphoma) was present in splenic tissues. Results of the current case study suggest that early exclusion of possible lymphoma is necessary in RDD patients who exhibit limited or no response to steroid therapy.