Background: Tumor-stroma ratio (TSR) is an independent prognosticator in colon cancer. Objective: We set out to investigate the predictive power, as well as to validate the prognostic power of TSR in stage II colon cancer patients. Better identification of patients who could benefit from adjuvant chemotherapy remains an important issue in stage II disease. Methods: TSR was microscopically determined on haematoxylin and eosin-stained primary tumor tissue slides of 212 patients who received either adjuvant chemotherapy or surveillance after curative resection in a prospective randomized clinical trial (ABCSG-91). Results: Stroma-high tumors were associated with significantly more cancer-related death ((CaDeath) HR 2.30, 95% CI 1.05−5.03; p=0.037) and significantly shorter distant recurrence-free survival ((DRFS) HR 2.32, 95% CI 1.10−4.87; p=0.027) compared to stroma-low tumors. Backward multivariate Cox-regression analysis demonstrated TSR as an independent prognosticator for DRFS (p=0.027) and CaDeath (p=0.031). TSR did not validate as a predictive biomarker; CaDeath (HR 0.87, 95% CI 0.18−4.17; p=0.87), DRFS (HR 0.76, 95% CI 0.17−3.36; p=0.71) and OS (HR 0.96, 95% CI 0.29−3.21; p=0.95) for the type of chemotherapy given in ABCSG-91. Conclusions: TSR, an easily applicable and inexpensive observer-based method, is an independent predictor of poor prognosis in stage II colon cancer. Predictive value for adjuvant 5-FU/leucovorin could not be demonstrated.