Gastric cancer (GC) is the second most lethal cancer world-wide, and the poor overall 5-year survival rate of <25 % for GC is largely due to both the late detection of this aggressive disease and limited effectiveness of current treatment options. Collectively, these observations underscore the need to identify new molecular targets (i.e., genes) to serve as biomarkers for early detection and/or treatment strategies to improve patient outcomes. While GC represents a growing number of cancers whereby deregulation of the immune system is linked to tumor initiation and progression, the identity of innate immune regulators with oncogenic potential in the host gastric mucosal epithelium remains obscure. Over the last couple of decades experimental mouse models for many cancer types have been widely used with great success to identify genes whose expression and/or mutation status infl uences tumorigenesis. Considering the recent mounting evidence for the role of innate immunity in the pathogenesis of infl ammation-associated cancers such as GC, much attention has focused on members of the Toll-like receptor (TLR) family, which are key components of the innate immune system primarily known to trigger infl ammatory responses upon pathogen detection. Here, we describe techniques used on genetic mouse models for GC to examine the role of specifi c TLR family members in the pathogenesis of GC.