Neurosyphilis is a dangerous and increasingly more prevalent sexually transmitted infection of the central nervous system caused by the bacterium Treponema pallidum that can present during the advanced stages of the disease (tertiary syphilis). Health care providers must remain vigilant in screening for syphilis in patients with high-risk behaviors as a delay in diagnosis and treatment may lead to symptom progression and debilitating sequelae years later. To date, there have been no published simulation case studies on neurosyphilis. This simulation case, based on a real patient encounter, is written for emergency medicine residents to diagnose and manage a patient presenting with the sequelae of neurosyphilis. This case was run for four separate iterations at a simulation center with two residents and an attending physician acting as confederates. Following the case, learners were provided with bedside debriefing, and a question and answer session. Based on post-simulation qualitative assessment, junior residents alone were less likely to perform a comprehensive integumentary exam without the presence of senior residents, although both groups failed to elicit pertinent sexual history until they discovered syphilitic lesions. After case completion and debriefing, all learners were able to demonstrate the understanding of the primary learning objectives.