Although the carcinogenesis of SCC with EM is not understood,[5] EM is closely related to alcohol intake and tobacco smoking.[[1], [3], [5]] Then, we examined genetic characteristics using next-generation sequencing (NGS). Keywords: endoscopic submucosal dissection (ESD); epidermalization; epidermoid metaplasia; squamous cell carcinoma (SCC) EN endoscopic submucosal dissection (ESD) epidermalization epidermoid metaplasia squamous cell carcinoma (SCC) 327 329 3 07/27/23 20230701 NES 230701 Abbreviations CNV copy number variations ESD endoscopic submucosal dissection EM epidermoid metaplasia IPCL intra-papillary capillary vessels NGS next-generation sequencing SCC squamous cell carcinoma Epidermoid metaplasia (EM) is relatively common in the oral cavity, but rare in the esophagus.[1] It is defined by a well-developed granular layer and overlying hyperorthokeratosis close to the epidermis.[1] EM is principally benign, but is sometimes associated with dysplasia but seldom associated with carcinoma in and around the EM.[[2], [4]] We want to report a very rare case with esophageal squamous cell carcinoma (SCC) resembling EM and we analyzed molecular characteristics of this lesion. EM is characterized by a well-developed granular layer and overlying hyperorthokeratosis resembling the epidermis.[1] EM is essentially benign, but is seldom associated with SCC in and around the EM.[[2], [4]] Therefore, he underwent ESD and the resected whitish tumor measured 23 × 22 mm after formalin fixation. [Extracted from the article]