The recently published 2021 guidelines for the management of patients with anaplastic thyroid cancer from the American Thyroid Association provide updated recommendations and guidance for the treatment of this rare but lethal thyroid cancer and incorporate significant advances since the initial guidelines were published in 2012. In particular, the focus on prompt cytopathologic and immunohistochemical diagnosis with the identification of potentially actionable genomic/molecular targets affirms the central and key role of pathologists and cytopathologists in not only the diagnosis but also the management of these patients.