Thirty to 40,000 patients develop cancer of the upper aerodigestive tract each year. This group comprises approximately 5% of all cancers. The most common type is squamous carcinoma, arising in the mucous membranes of the larynx, hypopharynx, oropharynx, nasopharynx, and oral cavity. Survival after treatment for these cancers is usually very poor, but not necessarily because of recurrent disease. These patients are of advanced age with poor nutrition and many associated medical problems that adversely affect the patient’s longevity. In addition, because most of these patients have mucosal changes throughout their entire upper aerodigestive tract, “a field of cancerization,” they are at risk for the development of second carcinomas (1). The survival of approximately one third of these patients is a direct result of the biologic behavior of a second synchronous or metachronous primary cancer (2–4). The type of treatment given for the initial or “index” cancer has a major effect on how the second cancer is treated. There is no evidence that the use of radiation can prevent this phenomenon and, in fact, its previous use may compromise the ideal treatment for the subsequent cancer (5). Almost every paper published today dealing with the treatment of squamous carcinomas of the head and neck ends commenting on “the survival of patients with head and neck squamous carcinomas will not be markedly improved until the question of second cancers in the upper aerodigestive tract is addressed.” In any list of reasons for failure of treatment of a squamous carcinoma of the head and neck, the following are considered: local regional failure, distant metastasis, complications of treatment, intercurrent disease, and second primary cancers. The problem with second primary cancers has been around a long time and, in fact, in an autopsy series in 1932 that consisted of 1078 examinations of cancer patients, multiple cancers were found in 40, which represented 3.7% (6).KeywordsEsophageal CancerPrimary CancerSquamous CarcinomaAerodigestive TractLaryngeal CarcinomaThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.