Kikuchi-Fujimoto disease (KFD) is an infrequent benign self-limiting disease predominantly affecting young Asian women and has an excellent prognosis. Diagnosis of KFD is confirmed by characteristic immunohistology of lymph node biopsy revealing histiocytic necrotizing lymphadenitis with abundant CD 68+ plasmacytoid monocytes in the paracortex and karyorrhectic debris. SLE, in particular, has been reported to precede, occur simultaneously, or appear after KFD. Treatment modalities and clinical outcomes of both KFD and SLE are vastly different. Hence, it is imperative to make timely correct diagnoses of SLE and treat early to avoid multi-organ failure and potentially fatal outcomes. The case report is presented of a challenging case of a 26-year-old Asian male who was initially diagnosed with KFD, and subsequently met the diagnostic criteria for SLE. He was treated for SLE for 6 months and showed dramatic improvement symptomatically without any further recurrence.