Anaplastic carcinoma of the thyroid gland (ACT) is a rapidly growing neoplasm with a very poor prognosis. In this study, we examined an ACT with osteoclast-like giant cells expressing matrix--degrading cysteine proteinases and their endogeneous inhibitor cystatin C. Bronchoscopic evaluation of a 50-year-old man suffering from hoarseness, dysphagia, and dyspnea revealed an irregular tumor mass infiltrating into the trachea and the cricothyroid ligament region. On histological examination, a necrotizing undifferentiated anaplastic carcinoma with osteoclast-like giant cells was detected. An immunohistochemical study of the tumor tissue was performed using a panel of 15 antibodies, including double labeling techniques. Most of the osteoclast-like multinucleated giant cells (MGC) expressed CD68 and cathepsin K. Colocalization of cathepsin B and its endogenous inhibitor cystatin C occurred in the majority of MGC. Mononuclear cells (MC) were positive for cathepsin B, cystatin C, and CD 68, but only faintly for cathepsin K. Expression of cathepsins B and K in the MGC of the ACT might contribute to the invasive behavior of this tumor, thus promoting metastatic ability and destruction of the cartilagenous trachea.