INTRODUCTION: Much has been written about melanosis coli; in contrast, occurrences of pigmentation in the upper gastrointestinal (GI) tract remains relatively rare. Pseudomelanosis duodeni (PD) appears as a striking black-brown speckle across the mucosa, presenting a diagnostic challenge to endoscopists. The paucity of reported cases and minimal understanding makes management arbitrary. Follow-up data on the persistence of these accumulations and its long-term outcomes remain to be explored. CASE DESCRIPTION/METHODS: An 86-year-old female presented with fatigue, dizziness, and melena. She had a history of end-stage renal disease requiring hemodialysis, valvular heart disease, history of recurrent GI bleeding, anemia, and diabetes mellitus. Home medications included amlodipine, carvedilol, hydralazine, insulin (detemir and aspart), and oral iron supplements. On arrival, her vitals read BP – 156/49, HR – 78, RR – 18, Temp – 36.8°C, with an oxygen saturation of 93% on room air. The initial workup was notable for hemoglobin of 7.1 g/dL, from her baseline of 10.1 g/dL. She was transfused red cells and underwent an esophagogastroduodenoscopy (EGD), revealing multiple areas of blackish discoloration in the duodenum. Histology revealed accumulations of black pigment within macrophages in the lamina propria with villous blunting. Dialysis was resumed with darbepoetin alfa support. Once hemoglobin was stable, enteral feeding was restarted, and the patient was discharged without any medication changes with close follow-up. An extensive chart review revealed numerous EGDs in the past for similar presentations, demonstrating the gradual expansion of the speckled areas that were first noted after the initiation of dialysis four years prior. Figures 1 and 2 show the successive change. DISCUSSION: Despite being a recognized entity, much about pseudomelanosis duodeni remains unknown. In our patient, her long-standing pseudomelanosis can be attributed to chronic use of hydralazine, iron supplements, or worsening chronic renal disease requiring dialysis, all of which have been strongly implicated in the literature. This case demonstrates its ability to grow within months, and continue to persist for years, seen on serial EGDs. Altered metabolism patterns of pigments can explain its emergence after initiation of dialysis as renal function declines. Its clinical significance remains largely unknown, and no known complications or associated deaths have been reported.Figure 1.: Esophagogastroduodenoscopy (EGD) four years prior to current admission revealing an unaffected duodenal segment.Figure 2.: Esophagogastroduodenoscopy (EGD) from the most recent admission revealing black speckling consistent with pseudomelanosis duodeni.