A very brief introduction into some aspects of peripheral immune mechanisms is provided to elucidate the arguments of the regional cancer field model, which proposes that the tolerogenic immune responses to peripheral tissue and cancer antigens export the local cancer field to the draining lymph nodes. Knowledge of the anatomical connections between the tumor bed and the modular network of the lymphatic system is crucial for identifying lymph nodes at risk of being colonized by competent clonogenic carcinoma cells that form metastases. Although the development of the lymphatic system provides clues for deciphering the complexity of the regional lymphatic network, the topographical pattern analysis of a high number of nodal-positive carcinomas is necessary to define the lymph node regions representing first-, second-, and third-line lymphatic defense lines for a distinct local tumor site.