Leiomyosarcoma is a relatively uncommon mesenchymal tumor that exhibits smooth-muscle differentiation. We report a new case of leiomyosarcoma involving the tongue of a 67-year-old male. Histologically, the tumor was composed of variably oriented fascicles of spindle-shaped cells with 'cigar-shaped' nuclei and eosinophilic cytoplasm, containing occasional PAS-positive granules. Atypical mitotic figures and necrotic foci were frequently detected. Consistent desmin, alpha-smooth muscle-specific and sarcomeric actin, and vimentin immunoreactivity was demonstrated in the tumor cells, whereas cytokeratins, CD 30, CD 31, CD 34, CD 45, CD 68, EMA, GFAP, HMB 45 and S-100 protein were negative. The patient underwent wide surgical excision of the tumor and is alive and disease-free at a 5-year follow-up. This report emphasizes the difficulties in the differential diagnosis of these uncommon tumors in an intra-oral location.