Recent investigations employing whole-genome sequencing and whole-exome sequencing have revealed mutations in multiple genes, including TP53, CDKN2A, FAT1, NOTCH1, PIK3CA, KMT2D, and NFE2L2, previously linked to esophageal squamous cell carcinoma (ESCC) (Sasaki et al., 2016). The gene discussed is NOTCH1; the disease is esophageal squamous cell carcinoma.