Introduction Granular cellular tumors are unusual lesions that can occur in the gastrointestinal tract, where they localize most commonly to the esophagus followed by the colon. Areas Covered We report a case of a young man with a sub-epithelial lesion of the ascending colon, removed by endoscopic submucosal dissection. Histological examination revealed a granular cellular tumor without features of malignancy. We present a systematic review of the English literature evaluating granular cellular tumors of lower gastrointestinal tract. Expert Commentary These tumors are usually asymptomatic and discovered incidentally during endoscopy performed for other reasons. Though their histological behavior is usually benign, 1–2% are malignant. Therefore, it is important that these lesions are excised and adequately pathologically characterized.