Neuropsychiatric systemic lupus erythematosus (NPSLE) presents a diagnostic challenge as there is no unified pathophysiological process driving its presentation. Case reports are limited in detailing manifestations and outcomes of NPSLE. This case highlights a unique presentation of NPSLE and discusses challenges associated with diagnosis. A 27-year-old man with systemic lupus erythematosus presented with altered mentation. Initial laboratory results and computed tomography of the brain were unremarkable, but magnetic resonance imaging of the brain revealed ring-enhancing lesions reported as NCC. This led to an extensive infectious disease evaluation, but ultimately there was no evidence of infection. The patient was diagnosed with NPSLE; treatment with intravenous glucocorticoids and cyclophosphamide led to dramatic clinical improvement. Repeat brain magnetic resonance imaging showed resolution of the ringed lesions. This case illustrates the importance of thorough evaluation in immunocompromised patients and warns of the risk of anchoring bias that can lead to diagnostic delays.