Hypothyroidism is a common disease that is easily treated in the majority of cases, when readily diagnosed; however, presentation of an aggregate of its symptoms is often clinically overlooked or attributed to another disease and can potentially be lethal. Already prevalent in older women, its occurrence in younger patients is rising as a result of radiation therapy, radioactive iodine therapy, and newer antineoplastic agents used to manage various malignancies. The presence of nonspecific constitutional symptoms and neuropsychiatric complaints in cancer patients can be attributed to a myriad of other diagnoses and therapies. Thyroid dysfunction can be easily overlooked in cancer patients because of the complexity of cancer's clinical picture, particularly in the pediatric population. Underdiagnosis can have important consequences for the management of both hypothyroidism and the malignancy. At minimum, quality of life is adversely affected. Untreated hypothyroidism can lead to heart failure, psychosis, and coma and can reduce the effectiveness of potentially life-saving cancer therapies, whereas iatrogenic causes can provoke atrial fibrillation and osteoporosis. Consequently, the diagnosis and treatment of hypothyroidism in cancer patients are pertinent. We summarize the history, epidemiology, pathophysiology, clinical diagnosis, and management of hypothyroidism in cancer patients. The Oncologist 2014;19:34-43Implications for Practice: Clinicians should be aware of the role that hypothyroidism can play in the diagnosis, treatment, and recovery of cancer. Because the myriad of symptoms associated with hypothyroidism can easily be attributed to the initial malignancy, to chemotherapy or radiation therapy, or to cancer recurrence, it is easy to miss the diagnosis of hypothyroidism. Timely diagnosis and treatment is necessary to minimize the complications of hypothyroidism, to optimize cancer therapy, and to minimize recurrence.We highlight newer therapies associated with hypothyroidism and the negative impact that hypothyroidism can have in patients with a malignancy.