This study advances an emerging paradigm in colorectal cancer cell detection and eradication, employing GCC as a molecular marker and immunological target. GCC is a protein whose expression is normally restricted to intestinal epithelial cells, but universally expressed by metastatic colorectal tumors. We have clinically validated the detection of occult metastases in lymph nodes by quantifying GCC mRNA (messenger RNA) by reverse transcriptase (RT)-PCR (qRT-PCR). This study revealed that occult metastases were the most powerful independent predictors of survival in pN0 patients. Further, there is a disproportionate burden of occult disease in African American, compared to Caucasian, patients. This new molecular staging platform provides a unique opportunity to identify occult metastases underlying racial disparities in disease recurrence, which could be prevented by tumor-targeted immunotherapy.