The greater omentum contains abundant lymphoid tissues composed of a lot of macrophages and lymphocytes, and plays an important role in a host defense system in the peritoneal cavity. Also, it is well known to be an initial site of peritoneal disseminated metastases. We experienced a rare case of a 60-year-old man with postoperative recurrence of esophageal cancer that presented itself in the greater omentum of the gastric tube reconstructed through a mediastinal route, as well as through mediastinal lymph-nodes. We performed CT-guided radiofrequency ablation (RFA) for recurrent omental tumor that was refractory to chemoradiation therapy and growing rapidly adjacent to the trachea. In combination with local control using RFA, we attempted a systemic immunotherapy using OK-432, by subcutaneous injection around RFA to accelerate host antitumor immune responses induced by antigen stimulation by RFA, based on the immunological property of the omentum. RFA induced a significant therapeutic effect on the omental tumor with massive necrotic change. However, no apparent size reduction was seen in the metastatic mediastinal lymph nodes, although an increase of peripheral blood lymphocytes was observed before and after RFA, and systemic host immune responses were stimulated by OK-432.