Clinicopathologic associations of EZH2, a transcriptional repressor that induces H3K27 tri-methylation (H3K27me3), have been drawn in many cancer types, including breast cancer, non-small cell lung cancer (NSCLC), colorectal cancer, endometrial cancer, gastric cancer, prostate cancer, ovarian cancer, and squamous cell carcinoma of the head and neck (SCCHN). Here, EZH2 is linked to head and neck squamous cell carcinoma.