Metastatic disease to the stomach or duodenum is an infrequent diagnosis, with prior autopsy studies estimating the incidence of gastric metastases to be 0.2-5.4%. Head and neck squamous cell carcinoma (HNSCC) is one of the least common primary malignancies that lead to gastric or duodenal metastases. We report a rare case of UGIB secondary to metastatic HNSCC to the stomach and duodenum in a patient with concurrent HIV infection. A 65-year-old man with HIV (CD4 count 354) on anti-retroviral therapy and HNSCC for which he was status post chemotherapy, radiation, and bilateral neck dissection, presented to the emergency department with melena. He was found to have a normocytic anemia (Hb 6.8) and benign abdominal exam. Rectal examination was significant for melena. Esophagogastroduodenoscopy revealed numerous cratered nodules with contact bleeding in the stomach (Figure 1) as well as the duodenum (Figures 2, 3) that appeared malignant. No active bleeding was observed and no additional endoscopic therapy was performed. Biopsies of both the gastric and duodenal nodules revealed metastatic squamous cell carcinoma. The patient was transfused multiple units of packed red blood cells and was eventually discharged to home hospice. The incidence of gastric metastases varies in the literature, ranging from 0.2%-5.4% in prior autopsy studies. As uncommon as gastric metastases from HNSCC are, duodenal metastases are even less common. A 2010 review of all reported cases of HNSCC metastases to the small bowel yielded a total of twelve cases. The rarity of HNSCC metastases to the duodenum highlights the unique nature of our case. Prior studies examining the relationship between HNSCC and HIV infection revealed that patients with HNSCC and concurrent HIV infection have an earlier age of onset and an overall poorer prognosis. There is a paucity of data regarding the pattern of metastatic disease in patients with HNSCC and HIV. However, it can be postulated that defects in local immune surveillance in patients with HIV may result in an increased likelihood of distant metastases, including metastases to the GI tract. Our review of the literature did not reveal any other published cases of primary HNSCC with synchronous gastroduodenal metastases. The pattern of metastatic disease in HNSCC raises the question of whether immunocompromise in the setting of HIV infection increases the likelihood of distant metastasis; however, further studies are needed to evaluate this possibility.Figure: Cratered nodule with contact bleeding (bottom left) and PEG tube site (top right).Figure: Cratered nodules with contact bleeding in the second portion of the duodenum.Figure: Cratered nodules in the second portion of the duodenum.