The transcription factor, c-Myc, has been implicated in many human cancers, although it's role during gastric tumourigenesis and progression remains unclear. In our laboratory, we have generated a well characterized mouse model of gastric cancer, called the gp130Y757F (gp130F/F) mouse. The mutation carried by gp130F/F knock-in mice prevents Socs3-mediated inhibition, resulting in the development of Stat3-driven gastric adenomas that are associated with increased c-Myc expression. To determine the function of c-Myc in gastric cancer progression we employed gp130F/F compound mice that express the gastric tumor-specific, tamoxifen (Tmx) dependent Cre (A33CreERT2) and conditional c-Myc alleles. Importantly, as the activity of A33CreERT2 is inducible, c-Myc can be deleted in established tumors. To assess the contribution of c-Myc expression to growing tumors, 60 day old gp130F/F; A33CreERT2; c-Myclox/lox compound mice were treated with Tmx and analysed 90 days later. We found that conditional deletion of c-Myc specifically in tumors of gp130F/F; A33CreERT2; c-Myclox/lox mice resulted in a 2-fold reduction of tumor burden when compared to gp130F/F; c-Myclox/lox that lacked expression of A33CreERT2. To confirm the deletion of c-Myc in gastric tumors of these mice, we assayed for c-Myc by quantitative PCR and Western blot and observed a robust deletion of c-Myc at the transcript and protein levels. Next we generated gp130F/F; c-Myc+/- mice in order to investigate whether partial inhibition of c-Myc activity was sufficient to impact upon tumor burden. We found that gp130F/F; c-Myc+/- had approximately a 2-fold reduction in tumor burden compared to gp130F/F; c-Myc+/+ littermates. Therefore, c-Myc plays a critical role in the progression of Stat3-dependent gastric tumors, and indentifies c-Myc as a desirable drug candidate for the treatment of gastric cancers in the clinic.