A 48-year-old woman was admitted to our hospital with abdominal fullness and pain. A barium enema and endoscopy revealed a Borrmann type II-like tumor of the sigmoid colon. Biopsy specimens showed poorly differentiated adenocarcinoma. Sigmoidectomy with lymph nodes dissection was performed. The tumor histologically consisted of proliferation of large and polygonal cells showing an organoid, trabecular or rosette-like pattern. Many mitotic figures were also observed. The tumor cells were immunohistochemically positive for chromogranin A. These findings led us to a diagnosis of large cell neuroendocrine carcinoma (LCNEC). Six months after surgery, liver metastases, para-aortic lymph node metastases and local recurrence were identified, and we commenced to administer FOLFOX, a combination of l-leucovorin and 5-fluorouracil with oxaliplatin. After six courses, a partial response was observed. This entity of the colon is not clearly recognized at present. The clinicopathological characteristics of LCNEC of the colon must be defined so that an appropriate treatment can be developed. Since LCNEC of the lung has been reported to be of high-grade malignancy, LCNEC of the colon must be treated as potentially highly malignant. In addition, the present case suggested that FOLFOX is a promising treatment for LCNEC of the colon.