RELN (Reelin) is an extracellular glycoprotein that plays a critical role in neuronal migration. Here we show that the RELN gene is frequently silenced in gastric cancers (GCs) by aberrant promoter hypermethylation. Although RELN was strongly expressed in non-tumor gastric epithelia, its expression was weak, or absent, in GC cell lines and primary GC tumors. Absence of RELN expression significantly correlated with a more advanced stage of GC. Methylation of the RELN promoter was frequently found in GC cell lines and in primary GC tumors. These findings suggest that disruption of the RELN pathway may be involved in gastric carcinogenesis.