Abstract Background OPCML belongs to the IgLON family of Ig domain–containing GPI-anchored cell adhesion molecules and was recently found to be involved in carcinogenesis, while its role in gastric cancer remains unclear. Methods We assessed expression and biological behavior of OPCML in gastric cancer. Results OPCML expression was markedly reduced in tumor tissues and cancer cell lines. Decreased OPCML expression had a significant association with unfavorable tumor stage (p = 0.007) and grading (p