This study aimed to analyze the molecular characteristics of gastric adenocarcinoma of the fundic-gland type (GAFG) and explore the possible mechanism of tumor development. Samples from 10 Chinese patients with GAFG were collected at the Peking University International Hospital and Liaocheng People's Hospital between January 2015 and March 2022. The nucleic acid sequence of Epstein Barr virus-encoded RNA (EBV-EBER) was detected by
in situ
hybridization. Genetic mutation information for
GNAS
,
KRAS
,
NRAS
,
BRAF
,
PIK3CA
,
TP53
,
APC
,
CTNNB1
,
HER2
,
MLH1
,
MSH2
,
MSH6
, and
PMS2
was obtained by Next-Generation Sequencing, and the relevant literature was reviewed. A total of eight instances of missense mutations were detected, consisting of seven cases with
GNAS
mutations, two cases with
KRAS
mutations, and one case with a
TP53
mutation. Additionally, two patients had simultaneous missense mutations in
GNAS
and
KRAS
. Nonsynonymous mutations in
APC
,
CTNNB1
,
NRAS
,
BRAF
,
PIK3CA
,
HER2
,
MLH1
,
MSH2
,
MSH6
, or
PMS2
were not observed in any cases. In addition, all tumors were EBER-negative. GAFG exhibits diversity at the molecular level, and
GNAS
mutations are more common than
KRAS
mutations,
TP53
mutations, and microsatellite instability. To date, no association between EBV/
HER2
and GAFG has been found.