Sentinel lymph node sampling may be studied profitably in series of patients with 1 tumor type, such as breast carcinoma, in 1 anatomic locale. The present work analyzes the efficacy of sentinel node sampling in a pathologically diverse group of lesions from an anatomically diverse region such as the head and neck; however, there are risks conflating the findings in different tumors with radically different behaviors, in the process producing muddled data. This report reviews the head and neck experience with sentinel sampling and concludes that certain tumor types that have a known propensity for aggressive behavior are the best candidates for trials employing sentinel node sampling; candidates include many cutaneous melanomas of the head and neck, oropharyngeal squamous carcinomas, and selected thyroid carcinomas. Despite the growing popularity of sentinel node sampling in a variety of regions of the body, however, at this juncture this technique remains an investigational procedure, pending demonstration of a tangible improvement in patient outcome through its use. It is recommended that studies of the efficacy of this technique strive, whenever possible, to segregate results of different tumor types in different head and neck locales from one another so as to produce more focused findings for discrete types of malignancies, and not group together tumor types that may in reality exhibit different biological behaviors.