We report a rare and severe nasal presentation of antiphospholipid syndrome in a 41-year-old man with systemic lupus erythematosus and end-stage renal disease. His nasal signs included total septal necrosis, along with external nasal swelling and erythema. Prior to the correct diagnosis, multiple medical and surgical treatments were attempted without success. After initiation of intravenous immunoglobulin and anticoagulation therapy, his nasal symptoms promptly resolved. The nasal complication of antiphospholipid syndrome is a relatively unknown and rare finding with limited discussion in the otolaryngology literature.