Introduction: Malignant fibrous histiocytoma (MFH) is a tumor which has a mesenchymal origin, and an uncertain histogenesis. MFH with giant cell accounts for 3-15% of all malignant fibrous histiocytomas. Objective: To explore the histopathology, the diagnosis and the treatment of MFH with giant cell of larynx. Patient and Methods: We report a case of a glottic MFH at a 59-year-old male, who has been smoking for 30 years, and was hospitalized in June 2008 at Emergency County Hospital of Craiova. Results: The largely-sized tumor was originated in glottic area, upper a left vocal cord, with no paresis. The tumor determined respiratory failure and dysphonia. Patient underwent surgical excision of the tumor after an emergency tracheotomy. The immunohistochemical techniques proved positive for vimentin, smooth muscle actin, CD68, CD34, bcl2, EGFR, S100, Ki67, and negative for CD117, NFT, chromogranin, c-erbB2, CK34betaE12, MNF116, and p53. Conclusions: Malignant fibrous histiocytomas (MFH) with giant cell of larynx are very rare mesenchymal neoplasm (this case seems the first reported). The diagnosis of MFH of larynx was difficult and the immunohistochemistry could have been helpful.