All esophageal small-cell carcinomas exhibited diffuse and uniformly strong immunopositivity of p16, whereas high-grade squamous cell carcinomas demonstrated a diffuse and strong pattern in one case (1%), a focal positivity in 5 cases (6%), and a single-cell positivity in one case (1%). Here, CDKN2A is linked to esophageal small cell neuroendocrine carcinoma.