Radical gastrectomy for gastric cancer with D2 lymph node dissection has been widely applied in advanced gastric cancer. It is believed that such surgery should extremely sweep away local-regional tumor tissues and cancer cells and thoroughly prevent tumor recurrence in situ. However, for most patients with advanced gastric cancer, tumor local-regional recurrence has been proven unavoidable. This study has found that isolated cancer cells, separate from the primary lesion and lymph nodes, existed in the mesogastrium of resected gastric cancer specimens, leading to the hypothesis that these cancer cells may have infiltrated the mesogastrium through a fifth metastasis route (here named Metastasis V) which is distinct from the other four classic metastasis routes, and cannot be resected by conventional radical gastrectomy with D2 lymph node dissection. Local-regional recurrence might be closely associated with these cancer cells in the mesogastrium, and therefore, complete mesogastrium excision (CME) should be imperative and become the third radical principle for radical gastrectomy. (C) 2012 Elsevier Ltd. All rights reserved.