Abstract Introduction/Objective Syphilis, a sexually transmitted disease that is caused by spirochete Treponema pallidum, can vary widely in presentation. Infective lymphadenitis due to syphilis have been reported before in cervical and inguinal lymph nodes.Here we present an interesting case of syphilitic lymphadenitis with unusual presentation and location. Methods/Case Report A 30-year-old male with no past medical history presented with epigastric pain, fever, jaundice, weight loss, and night sweats. Computed tomography imaging revealed a 4.1 cm solid mass at the porta hepatis with involvement of perihepatic lymph nodes, raising suspicion of malignancy. All serological tumor markers were negative. The patient underwent ERCP with biliary drainage to relieve obstructive jaundice. Bile duct brushing and liver biopsy at that time were non-diagnostic. Later the patient underwent laparoscopic lymph node excision. Histological examination of the lymph node showed intact follicular architecture with an increase in plasma cells and sinus histiocytes, without evidence of carcinoma or lymphoma cells. Flow cytometry on the lymph node showed polytypic B-cells and antigenically normal T-cells with CD4: CD8 ratio of 0.5 showing relatively excess of CD8 positive cytotoxic cells. Positive staining for Treponema pallidum with appropriate control highlighted micro-organisms suggestive of secondary syphilitic infection. This evidence was later supported by positive rapid plasma reagin (RPR) test. He subsequently tested positive for Human immunodeficiency virus (HIV-1). Results (if a Case Study enter NA) NA Conclusion In summary, appropriate histologic and serological testing lead to timely diagnosis in this case. This case contributes to the limited literature on syphilitic lymphadenitis and reports the first documented case of isolated intra- abdominal lymph node involvement.