Aims:  To determine the clinicopathological and molecular features of gastric medullary cancer.

Methods and results:  Clinicopathological review and microsatellite instability (MSI) analysis were carried out on 17 gastric medullary and 64 non‐medullary cancers. In addition to characteristic histopathology, gastric medullary cancers had certain prominent features: (i) the average survival time was longer in medullary and low‐grade non‐medullary cancers than in high‐grade (P = 0.004); (ii) serosal involvement was less common in medullary cancers (29.4%, 5/17) than in non‐medullary cancers (9.4%, 6/64) (P < 0.05) while pushing borders were more common in medullary cancers (70.6%, 12/17 versus 17.2%, 11/64, P = 0); (iii) the presence of intraepithelial lymphocytes (IELs) in medullary and non‐medullary cancers was 2380/10 high‐power field (HPF) and 147/10 HPF (P = 0), respectively. Both peritumoural infiltrating lymphocytes (pTIL) and a Crohn's‐like reaction were more common in medullary cancers than in non‐medullary (pTIL 35.3%, 6/17 versus 3.1%, 2/64; a Crohn's‐like reaction 70.6%, 12/17 versus 32.8%, 21/64; P < 0.05); (iv) medullary and high‐grade non‐medullary cancers were more associated with reduced ECD expression in comparison with low‐grade cancers (P < 0.05); (v) higher MSI‐H (Bat26+) rate was observed in medullary cancers (41.2%, 7/17) than in non‐medullary (1.6%, 1/64) (P = 0).

Conclusions:  Gastric medullary cancer has distinct clinicopathological features and genetic alterations. Two subtypes of gastric medullary cancers, Bat26+ and Bat26–, might have prognostic implications, thus analysis of Bat26 may be of clinical value.