Gastric amphicrine carcinoma (GAC) is a rare malignancy exhibiting dual neuroendocrine and exocrine differentiation. Claudin 18.2 expression patterns in GAC remain poorly characterized. We retrospectively analyzed four GAC cases diagnosed between 2020 and 2024 were retrospectively analyzed. Diagnosis required expression of at least two neuroendocrine markers and intracellular mucin, with amphicrine components comprising >30 % of tumor. Immunohistochemical evaluation included neuroendocrine markers, HER2, and Claudin 18.2. All patients were males aged 52–72 years (mean: 61.5 years). Tumors were located in gastric antrum (n = 2), cardia (n = 1), and body (n = 1), ranging from 4.0 to 4.5 cm. Three morphological patterns were identified: sheet-like/nested, tubular, and signet-ring trabecular. All cases expressed synaptophysin, with variable expression of chromogranin A (3/4), INSM1 (2/4), and CD56 (3/4). HER2 was negative in all cases. Claudin 18.2 expression correlated with morphological patterns: moderate to strong staining in sheet-like/nested areas (3/4) and tubular structures (3/4), but absent in signet-ring trabecular components (2/4). Follow-up demonstrated hepatic metastasis (n = 1) and death (n = 1) at 6 months, while two patients remained alive without recurrence. GAC may demonstrate distinctive morphology-dependent Claudin 18.2 expression, suggesting potential implications for targeted therapy selection and molecular subtyping. The morphological heterogeneity and aggressive clinical behavior underscore the importance of accurate diagnosis through comprehensive integrated assessment.