Background: According to the DESTINY-Breast04 trial, treating patients with breast cancer and low human epidermal growth factor receptor 2 expressions (HER2-low) varies from that of those with no HER2 expression. However, it is interesting to know if HER2-low indicates for anti-HER2 therapy in the gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Hence we conducted this study to assess the incidence, clinicopathological features, and treatment outcomes of patients with HER2-low G/GEJ adenocarcinoma., Patients and Methods: This was a single-center, retrospective observational study. Patients with previously untreated G/GEJ adenocarcinoma were classified based on their HER2 status using immunohistochemistry (IHC) with or without in situ hybridization (ISH) as follows: HER2 negative (IHC 0), HER2-low (IHC 1+ or 2+/ISH-), and HER2-positive (IHC2+/ISH+ or 3+)., Results: In total, 734 patients with G/GEJ adenocarcinoma were divided into three groups (HER2-negative, n = 410; HER2-low, n = 154, and HER2-positive, n = 170). The intestinal-type histology, peritoneal metastasis, and higher serum carcinoembryonic antigen (CEA) levels differed significantly among patients with negative, low, and positive HER2 statuses: intestinal-type histology (21.0%, 44.2%, and 59.8%, respectively), peritoneal metastasis (56.3%, 44.8%, and 21.8%, respectively), and higher serum CEA level (32.2%, 41.6%, and 56.5%, respectively). Improved survival was observed in the HER2-positive group than in the HER2-negative G/GEJ adenocarcinoma group [hazard ratio (HR) = 0.73, 95% confidence interval (CI) 0.59-0.89; P = 0.002]. However, the prognoses of the HER2-low and HER2-negative groups were similar (HR = 1.01, 95% CI 0.82-1.23; P = 0.843)., Conclusions: Patients with HER2-low G/GEJ adenocarcinoma exhibited intermediate and distinct characteristics than those in the HER2-negative group. Similarly, the HER2-low group's prognosis was worse than that of the HER2-positive group. Therefore developing novel therapeutic strategies targeting HER2-low G/GEJ adenocarcinoma is required., Competing Interests: Disclosure DT has received fees from Taiho Pharmaceutical Co., Ltd, Eli Lilly Japan K.K, and Bristol-Myers Squibb Japan. ES has received Honoria from Taiho Pharmaceutical Co., Ltd, Sanofi, Eli Lilly Japan K.K, Takeda Pharmaceutical Co., Ltd, Merck Serono Co., Ltd, Chugai Pharmaceutical Co., Ltd, Daiichi-Sankyo Co., Ltd, and Ono Pharmaceutical Co., Ltd. KY has received lecture fee from Chugai Pharmaceutical Co., Ltd, Merck Biopharma, Bristol-Myers Squibb Japan, Takeda Pharmaceutical Co., Ltd, Taiho Pharmaceutical Co., Ltd, Eli Lilly Japan K.K, Ono Pharmaceutical Co., Ltd, Sanofi, and Daiichi-Sankyo Co., Ltd. The Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research has received research funding from Ono Pharmaceutical Co., Ltd, Sanofi, Taiho Pharmaceutical Co., Ltd, Eli Lilly Japan K.K, and Yakult Honsha Co., Ltd. All other authors have declared no conflicts of interest. Data Sharing The data underlying this article will be shared on reasonable request to the corresponding author., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)