Abstract Background A giant cell tumor (GCT) is a benign neoplasm characterized by mixture of mononuclear cells and multinucleated cells. A GCT of soft tissue (GCT-ST) is developed in various extraosseous sites, but GCT-ST of the gastrointestinal tract is very rare. GCT-ST usually has a benign course, but rare cases reported malignant potential of the tumor. Therefore, complete resection is required to prevent local recurrence or distant metastasis. Case presentation A 53-year-old woman was admitted for follow-up colonoscopy who underwent the colorectal endoscopic submucosal dissection (ESD) of a laterally spreading tumor at the hepatic flexure 6 months ago. A colonoscopy showed a polypoid mass about 3.5 × 2.5 cm at the previous ESD site. As endoscopic finding showed a smooth multi-nodular tumor without submucosal invasion, we performed endoscopic mucosal resection. Based on pathological and immunohistochemical findings, the lesion was diagnosed as a GCT-ST in the colon. Follow-up colonoscopy performed 6 months later revealed no evidence of recurrence. Conclusion This is the first report of a GCT-ST identified in the colon. Although GCT-ST generally has a benign clinical course, complete resection should be performed to prevent local recurrence and metastasis.