BACKGROUND Ten percent of gastric cancer (GC) cases are familial, with one third resulting from a mutation in the tumor suppressor gene CDH1. Loss of this important structure can result in hereditary diffuse gastric cancer (HDGC), which carries a high mortality if early diagnosis is not made. Despite its clear genetic origin, optimal management of HDGC family members is controversial, as the utility and efficacy of current cancer screening programs for mutation carriers are unproven. METHODS A 53-year-old Caucasian woman was initially seen for genetic screening because multiple family members had mutations of the CDH1 gene. Her pedigree analysis demonstrated 4 generations of gastric cancer, and 2 of the generations carried the CDH1 germline mutation, consistent with HDGC. At endoscopy, the patient's gastric mucosa was normal and random biopsies were also normal. The patient underwent a laparoscopic total gastrectomy. RESULTS The gross examination of her stomach appeared normal. On histologic examination, however, the stomach was found to have diffuse (signet ring cell) adenocarcinoma in-situ with 11 microscopic foci of invasive adenocarcinoma limited to the lamina propria. CONCLUSION Our case is the first reported prophylactic total gastrectomy utilizing a laparoscopic approach, and it highlights the importance of taking a thorough family history and obtaining a pedigree analysis. Endoscopic screening in HDGC cannot rule out diffuse GC, because the stomach and biopsies can be normal despite the presence of adenocarcinoma. Therefore, our case supports the recommendation for prophylactic gastrectomy in HDGC.