A promising approach for cancer chemoprevention might be a combination therapy utilizing dietary phytochemicals and anticarcinogenic pharmaceuticals at a suboptimal dosage to minimize any potential adverse side effects. To test this hypothesis, various dosages of anthocyanin-rich tart cherry extract were fed in combination with suboptimal levels of the nonsteroidal anti-inflammatory drug sulindac to APCMin mice for 19 weeks. By the end of the feeding period, fewer mice that were fed the anthocyanin-rich extract in combination with sulindac lost more than 10% of body weight than mice fed sulindac alone. Mice that were fed anthocyanin-rich extract (at any dose) in combination with sulindac had fewer tumors and a smaller total tumor burden (total tumor area per mouse) in the small intestine when compared to mice fed sulindac alone. These results suggest that a dietary combination of tart cherry anthocyanins and sulindac is more protective against colon cancer than sulindac alone.