While histologic assessment of nodes is a component of all colon cancer staging paradigms, approximately 30% of patients with histology-negative nodes (pN0) die of disseminated disease reflected by occult nodal metastases. Undetected metastases are particularly important when considering racial disparities in colon cancer, where black subjects with pN0 disease exhibit the greatest differences in outcomes, with >40% excess mortality. Recently, guanylyl cyclase C (GCC), a protein normally restricted to intestinal cells, but universally expressed by colorectal cancer cells, was validated for detecting occult metastases. Indeed, occult tumor burden across regional lymph nodes estimated by GCC quantitative reverse transcription PCR identifies pN0 patients with near zero risk, and those with >80% risk, of unfavorable outcomes. Disproportionately high occult tumor burden in black patients underlies racial disparities in stage-specific mortality. These studies position the platform encompassing quantification of occult tumor burden by GCC quantitative reverse transcription PCR for translation, as a detect-treat paradigm to reduce racial disparities in colon cancer mortality.