Generally, the incidence of thyroid cancer increases with age. This is particularly true of tumors with an anaplastic or follicular histopathologic pattern and of the medullary carcinomas. The most common tumors, with a papillary histopathologic pattern, have a bimodal, age-specific incidence, peaking in the 30s and late in life. Thyroid tumors occur more than twice as frequently in women than men. In the United States, African Americans seem to be at lower risk than others. Wide variations in thyroid cancer prevalence at autopsy have been reported internationally, from 3% to more than 10% of thyroids that have not been exposed to radiation, with the highest rates reported in Japan. Approximately 25% of medullary carcinomas, which make up 5% to 10% of thyroid cancers, are familial.

The major identifiable risk factor for the development of thyroid cancer has been a history of external irradiation of the head and neck or exposure due to a nuclear reactor accident. External irradiation was used as early as 1907 to shrink an enlarged thymus in infancy. During the 1920s and subsequently until the 1950s, it was used extensively to treat enlarged tonsils and adenoids, cervical adenitis, mastoiditis, sinusitis, hemangiomas, tinea capitis, and acne. Concern about ill effects began to mount in 1950, when a history of neck irradiation was noted in 9 of 28 cases of childhood thyroid cancer, with a latency period of five or more years. Further documentation followed, and radiation to the neck was discontinued. In 1973, attention focused on the issue again when 40% of a series of adults with thyroid cancer were found to have a history of irradiation. Large studies indicated that more than 25 % of exposed persons had detectable thyroid abnormalities; the prevalence of cancer was estimated at 7% to 9%. Some radiation-exposed persons were at greater risk than others. Radiation during infancy appeared to be most carcinogenic, with cancer risk decreasing as age at the time of radiation increased. Although the threshold dose for cancer risk was low, the risk seemed to be greatly increased for persons who received multiple treatments. The exposed population at risk was substantial—estimates ranged from 1 to 2 million persons. With the aging of that cohort, the prevalence of iatrogenic risk for thyroid cancer and the incidence of irradiation-induced cancers have decreased substantially. However, exposures from nuclear accidents continue to be a source of concern, most recently in the Fukushima area of Japan and previously around Chernobyl in the former Soviet Union.

Medullary thyroid cancer arises from neuroendocrine C cells of the thyroid gland. Approximately 25% of cases are associated with inherited tumor syndromes such as multiple endocrine neoplasia (MEN) 2A (medullary thyroid cancer, parathyroid tumors, and pheochromocytoma), MEN 2B (medullary thyroid cancer, mucosal neuromas, pheochromocytoma, and marfanoid habitus), or familial medullary carcinoma. All familial forms are inherited with the pattern of autosomal dominance, with mutations in the tyrosine kinase protooncogene RET identifiable in 98% of cases. Medullary thyroid cancer has been the most common cause of death in patients with MEN 2. There is great potential for genetic testing, followed by prophylactic thyroidectomy of young children shown to be carriers of predisposing RET protooncogene mutations, to reduce mortality and morbidity for these patients.