Context: - The head and neck regions have complex anatomic structures. They are not exempted from the rare occurrences of highly unusual, diagnostically challenging malignant neoplasms and mimickers.
Objective: - To review and update the utility of immunohistochemistry and molecular biomarkers and to pursue diagnostic accuracy on selected rare neoplasms, especially some poorly differentiated malignancies.
Data sources: - Personal experience and information from the literature.
Conclusions: - Head and neck tumors include neoplasms originating from heterogeneous tissue. Using the selected clinical cases, this review illustrates a continuous development of emerging molecular-genetic techniques to assist in the interpretation of uncommon, often poorly differentiated, highly malignant neoplasms. The diagnostic results are appropriately transmitted to the oncologists, radiation oncologists, and surgeons to create a coordinated plan of care for patients with these unusual disorders affecting the head and neck.