Background <p>Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare hereditary gastric cancer syndrome linked to <i>APC</i> promoter IB variants and characterized by gastric polyposis. Its natural history and management are poorly defined. We sought to characterize the clinicopathological features of GAPPS and infer management guidelines.</p> Patients and Methods <p>We retrospectively analyzed individuals with GAPPS enrolled in a natural history study from January 2017 to September 2023. Demographics, pathogenic gene variants, endoscopic findings, and histopathology results were studied.</p> Results <p>Of 21 patients with GAPPS, 11 (52%) were male, and most were non-Hispanic white (71%). Median age at germline genetic testing was 44 years (range 12–75 years), and all individuals had a pathogenic variant in the <i>APC</i> promoter IB. Esophagogastroduodenoscopy (EGD) was performed in almost all patients (91%), with a median age of 37 years (range 12–75 years) at initial EGD. Gastric polyps carpeting the fundus and body with antral sparing were noted in all individuals. Gastric adenocarcinoma (<i>n</i> = 3), high-grade dysplasia (<i>n</i> = 7), low-grade dysplasia (<i>n</i> = 3), and benign fundic gland polyposis (<i>n</i> = 6) were demonstrated on endoscopic biopsies. Then, 43% (9/21) of patients underwent total gastrectomy (TG) at a median age of 44 years (range 15–63 years). Histopathology of final gastrectomy specimens demonstrated more advanced pathology compared with endoscopic biopsies in five of nine patients.</p> Conclusions <p>Given the challenge of effective endoscopic surveillance owing to extensive polyposis, and the risk of malignant transformation, prophylactic TG should be considered for patients with GAPPS. Longitudinal studies are needed to delineate lifetime cancer risk and clinical management guidelines.</p>