Aims <p>Insulinoma-associated protein 1 (INSM1) is a recently added nuclear marker for neuroendocrine differentiation. However, INSM1 expression in gastric neuroendocrine and non-neuroendocrine neoplasms has not been thoroughly investigated.</p> Methods <p>We examined INSM1 expression in 72 gastric tumors, including 22 gastric neuroendocrine tumors and 50 gastric non-neuroendocrine neoplasms. Synaptophysin and chromogranin immunostaining were also performed for all cases.</p> Results <p>For gastric neuroendocrine neoplasms, INSM1 immunostaining demonstrated excellent sensitivity (21/22, 95.5%), comparable to synaptophysin (22/22, 100.0%), but had lower specificity (32/50, 64.0%) compared with traditional neuroendocrine markers (synaptophysin (36/50, 72.0%) and chromogranin (42/50, 84.0%)). However, decreased expression of INSM1, measured by H-score, was frequently found among neuroendocrine carcinoma cases. Gastric non-neuroendocrine neoplasms frequently exhibited INSM1 positivity (18/50, 36.0%); however, in most cases (16/18, 88.9%), staining was focal (involving &lt; 10% of tumor cells). Tumor histologic subtype and grade may be associated with INSM1 expression.</p> Conclusions <p>INSM1 nuclear positivity in gastric neoplasms should be interpreted with caution. INSM1 should not be used as a stand-alone marker for determining neuroendocrine differentiation in gastric tumors. Histologic evaluation with concurrent use of traditional neuroendocrine markers is warranted to accurately demonstrate neuroendocrine differentiation and minimize false positivity and false negativity.</p>