If a cancer in the neck is so poorly differentiated that the pathologist is not able to assign squamous origin using a cytokeratin stain, a broader panel of immunohistochemical stains becomes important to differentiate squamous cell carcinoma from lymphoma, adenocarcinoma (thyroid or other), melanoma, neuroendocrine carcinoma, medullary thyroid cancer, salivary histologies, etc. Various immunohistochemical markers such as thyroglobulin, calcitonin, thyroid transcription factor-1 (TTF), Paired-box gene 8 (PAX8), S100 protein, human melanoma black 45 (HMB 45) can be used (69). The gene discussed is CALCA; the disease is melanoma.