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Russell body esophagitis/gastritis (RBG) is a rare gastrointestinal inflammatory condition characterized by accumulation of plasma cells containing dense eosinophilic cytoplasmic inclusions, i.e., Russell bodies. Herein, we report a case of RBG in a patient with a systemic inflammation background. A 61-year-old female presented with oral infection. Upper gastrointestinal endoscopy revealed patchy salmon-colored esophageal mucosa proximally to the gastroesophageal junction, suggestive of “Barrett’s esophagus”. Histologic examination of the biopsy tissue from the lower esophagus showed diffuse lymphoplasmacytic infiltration with abundant admixed enlarged plasma cells (Mott cells) containing bright eosinophilic, round, dense, homogenous inclusions (Russell bodies) in cytoplasm. Immunohistochemical study demonstrated membranous staining of CD138 in the Mott cells, while immunoglobulin light chain in situ hybridization revealed positivity of only kappa light chain, indicating kappa light chain restriction and clonality. A proton-pump inhibitor therapy was initiated, but the patient passed away due to generalized infection. Our case suggests that Russell body esophagitis/gastritis (RBG) can be a gastrointestinal presentation associated with acute systemic infection.