Pseudomelanosis duodeni is a rare benign condition that manifests endoscopically as diffuse, small brownish-black spots in the duodenal mucosa, and the histochemical findings show an accumulation of hemosiderin pigment in the duodenal villi's lamina propria. This condition produces no specific symptoms, and it may be reversible. The cause and natural history of the pigmentation have not been clarified, although it is associated with a variety of systemic illnesses and medications. We describe two cases of pseudomelanosis duodeni and the patients had histories of diabetes mellitus, hypertension, chronic renal insufficiency and specific medications. We also review the relevant medical literature on this rare condition. (Korean J Gastrointest Endosc 2009;39:374-378)