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Castleman disease is a heterogeneous group of disorders of lymphoid tissue. It can often mimic other autoimmune diseases or malignancies, presenting a diagnostic dilemma to attending clinicians. Systemic lupus erythematosus and Castleman disease share many clinical and biochemical features rendering a special diagnostic challenge. Herein, we report a case of a young female who initially presented with features of idiopathic multicentric Castleman disease, subsequently developed antinuclear antibody positivity, and fulfilled the criteria for the diagnosis of systemic lupus erythematosus. Following the commencement of treatment for systemic lupus erythematosus, she had a marked response with resolution of altered clinical and biochemical profile.