Knowledge of lymphatic involvement in patients with colorectal cancer is important in surgery and in the postoperative decision-making process. Fifty-eight patients with recurrent colorectal cancer underwent operation with the RIGS/(Radioimmunoguided Surgery) technology. Preoperatively, patients were injected with 1 mg monoclonal antibody (MoAb) CC49 (anti-TAG-72-tumor-associated glycoprotein) labeled with 2 mCi of iodine 125. Traditional surgical exploration was followed by survey with a gamma-detecting probe. Localization of MoAb on tumor was noted in 54/58 patients (93%). Traditional exploration identified 117 suspected tumor sites. With RIGS, 177 suspected tumor sites were detected. In 17 of the 58 patients (27.5%), at least one occult tumor site identified by RIGS was confirmed by pathology with hematoxylin & eosin (H & E) staining. This finding resulted in 16 major changes in surgical plan. RIGS performance varied between lymphatic and non-lymphatic tissue, with a positive predictive value (PPV) of 95.6% and negative predictive value (NPV) of 90% in non-lymphoid tissue compared to PPV of 40% and NPV of 100% in lymphoid tissue. In patients with tumors that localize, no RIGS activity in lymph nodes signifies no tumor, while decisions based on RIGS activity in lymph nodes requires H & E confirmation. Using this guideline, additional information acquired by RIGS can help the surgeon in making an informed decision during surgery and in planning postoperative therapy.