In this exploratory analysis of patients with stage III, resected colon adenocarcinoma treated in a prospective, randomized trial evaluating adjuvant FU/LV versus IFL (CALGB/Alliance 89,803), we evaluated the utility of ZNF331 promoter methylation as a prognostic and predictive biomarker. The gene discussed is ZNF331; the disease is colon adenocarcinoma.