Abstract Introduction/Objective Malakoplakia is a rare histiocytic disease caused by defects in phagocytic or degradative functions of histiocytes in response to gram negative coliforms (E. coli or Proteus) that results in chronic inflammatory state, followed by intracellular deposition of iron and calcium (known as Michaelis-Gutmann bodies). It’s more common in immunocompromised patients and the mean age at diagnosis is fifth decade. It occurs in all organs, common in GU tract, particularly bladder, but also seen in gastrointestinal tract (most commonly colon, followed by stomach and duodenum), central nervous system and female genital tract. In gastrointestinal tract, it can present as a polyp with diffuse mucosal involvement, submucosal thickening, and even may cause mass. Methods/Case Report A 60 -year-old male smoker presented to our hospital with history of colon polyps; colonoscopy revealed a 6 mm sessile polyp at the hepatic flexure. A biopsy was performed which showed numerous epithelioid histiocytes with granular eosinophilic cytoplasm, abundant Michaelis-Gutmann bodies and increased lymphocytes. Immunohistochemical stains showed diffuse positivity for CD68; and PAS stain was positive for histiocytic cytoplasmic granules. Based on this data, the diagnosis of Malakoplakia was confirmed. Malakoplakia is treated with antibiotics that concentrate in macrophages (quinolones or trimethoprim-sulfamethoxazole), antibiotics directed against E. coli, surgery and possibly discontinuation of immunosuppressive drug therapy. Results (if a Case Study enter NA) Malakoplakia, in this case, was presented clinically as a sessile colon polyp and histologically showed numerous epithelioid histiocytes with granular eosinophilic cytoplasm, with Immunohistochemical stains (CD68; and PAS stain) the correct diagnosis was made. Other presentations of Malakoplakia include diffuse mucosal involvement, submucosal thickening, or mass. Histologically, it may rarely be mistaken as signet ring carcinoma. These variable presentations in GU tract or colon can be interpreted as malignancy with consequent unnecessary interventions. Hence, awareness of Malakoplakia with careful histopathologic examination and the use of immunohistochemical studies are advisable in that cases. Conclusion We would like to emphasize that Malakoplakia can be clinically and histologically misdiagnosed as a malignant condition; therefore histopathologic and immunohistochemical studies are needed to correctly diagnose this entity.