BACKGROUND Syphilis has increased in prevalence in the United States by 72.7% from 2013 to 2017, with the highest rates recorded in men who have sex with men. There is an increased incidence of syphilis in patients with a concomitant HIV infection, estimated at a 77-fold increase. CASE REPORT This report documents an unusual case of neurosyphilis manifesting as syndrome of inappropriate antidiuretic hormone secretion (SIADH) in a 56-year-old man with HIV/AIDS. A 56-year-old man who has sex with men with HIV/AIDS presented with a 4-day history of periumbilical abdominal pain, nausea, and constipation. A physical exam revealed slowing of baseline cognition, but was otherwise unremarkable. Urine and serum osmolality studies were consistent with SIADH as defined by the Bartter and Schwartz Criteria: serum osmolality <275 mOsm/kg, urine osmolality >100 mOsm/kg, urine sodium >20-40 mmol/L, euvolemia, and no other cause for hyponatremia identified. He was fluid-restricted, with improvement in laboratory abnormalities, further supporting the diagnosis of SIADH. A diagnostic work-up included a CT abdomen/pelvis with perirectal lymphadenopathy, colonoscopy negative for malignancy, chest CT with lymphadenopathy, and a head MRI negative for intracranial processes. The patient was ultimately found to have positive results on rapid plasma reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests, and was diagnosed as having neurosyphilis. He underwent penicillin desensitization and received a 14-day course of penicillin G, with recovery of sodium to normal range on discharge. CONCLUSIONS Our case highlights SIADH as an initial presenting sign of neurosyphilis with HIV infection, which has only been documented in 2 prior case reports. Our case highlights the importance of recognizing atypical presentations of neurosyphilis in patients with HIV to prevent long-term complications.