The aim of this article is to describe a case of leiomyosarcoma of the mandible with immunohistochemical analysis that was useful in making the final diagnosis. A 40-year-old woman was referred to the Stomatology Clinic of Sao Paulo Tatuape Hospital, for evaluation of a lesion on the left side of the mandible. This lesion presented a fast growth in the last 6 months. Intraoral examination showed a firm, fixed, red colored mass measuring, approximately 60-mm in diameter. No lymph nodes involvement was found. The radiographic examination showed a lytic lesion showed ill-demarcated radiolucent with facial and lingual cortical bone destruction. Microscopic examination of the mandibular lesion showed a neoplasm composed by interlacing fascicles of spindle-shaped cells. Most of the cells presented a blut-ended elongated shape. A marked cellular pleomorphism was observed, represented by cells with irregular shape and abundant eosinophilic cytoplasm. Nuclei were large, hyperchromatic, either vacuoled or cigar-shape. The cytoplasm of the cells stained red with Masson s trichrome stain. Neoplastic cells expressed vimentin, smooth-muscle actin, HHF-35 and desmin. These findings were consistent with the diagnosis of leiomyosarcoma.