 Anaplastic thyroid carcinomas ATC are high grade neoplasms, which account for approximately 2 to 5 of primary malignant thyroid tumors but more than 50 of thyroid cancer deaths. Because therapies for anaplastic thyroid carcinoma are very limited with even early stage disease, new approaches for treating this devastating cancer are needed. Recently, imatinib mesylate Gleevec, formerly known as STI571, has been approved for the treatment of chronic myelogenous leukemia and for treatment of gastrointestinal stromal tumors, expressing the c-Kit tyrosine kinase. Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor PDGF and stem cell factor, c-Kit, and inhibits PDGF- and SCF-mediated cellular events. Recent data suggest that many if not most, anaplastic thyroid cancers express PDGF receptors, and that these receptors are functional. Additional preclinical work from Japan demonstrates that c-Abl is overexpressed in p53 mutateddeficient anaplastic thyroid carcinoma cell lines and that select inhibition of c-Abl activity by STI571 has a dramatic cytostatic effect in these cells. 