Purpose: Syphilis is a systemic infection that can involve any organ system. Esophageal and gastric syphilis have been reported infrequently and are a rare complication in HIV patients and their prevalence is unknown. We present a case of a 38-year-old African American male admitted to the hospital with two months history of epigastric fullness, and an unintentional 30 lb. weight lost. He noticed a red papular pruritic rash starting on the back which then spread to the whole body including palms and soles, thighs, arms and buttocks. The rash resolved over about 3 weeks. Past medical history was significant for anemia. Sexual history was pertinent for heterosexual and sex with men partners, and gonorrhea treated in the past. On examination the BP was 120/86, the HR: 104 beats per minute, the RR: 18. Patient was cachectic, with bitemporal wasting and pale mucosa. Abdomen was soft, non-distended, non-tenderness to palpation, no hepatomegaly or splenomegaly, no masses. Labs test showed: Hb: 9.2, Hct: 27.4 and MCV: 83fL. RPR: >1:512. Fluorescent treponemal antibody absorption test was reactive. HIV: positive with a CD4 count of 353. An esophagogastroduodenoscopy revealed two shallow ulcerations in the hard palate. In the mid esophagus at 25 cm another 1 cm shallow ulcer was noted. Stomach demonstrated thickened gastric folds with superficial erosions-ulcers in the antrum. Duodenal bulb and descending duodenum were within normal limits. An immunohistochemical stain for treponemal organisms was positive. Immunohistochemical and special stains were performed and were negative for herpes simplex virus, cytomegalovirus, and fungal organisms. Gastric and esophagus biopsy findings were consistent with syphilitic gastritis and esophagitis. The patient was diagnosed with esophageal and gastric syphilis, and a new diagnosis of HIV. The gastrointestinal symptoms of the patient improved after treatment with penicillin 24M units IV every 12 hours for 12 days. Esophageal and gastric syphilis should be considered in patients at risk for sexually transmitted disease, and with nonspecific symptoms like epigastric or abdominal pain-fullness, vomiting, weight loss, and early satiety. A wide variety of non-specific endoscopy findings have been reported with more than one lesion type, including shallow ulcers, nodularity, mucosal erosions, erythema, thickened folds, and deep ulceration. Gastric syphilis is a great imitator of other gastric diseases, therefore immunofluorescent test is required to identify treponema pallidum and prompt treatment with long- acting penicillin G is recommended.