Whole grains are nutrient rich and may protect against chronic disease. To study this, we previously reviewed 14 case-control studies of colorectal, gastric, and endometrial cancers and found consistently lower risk in those with high than in those with low whole-grain intake. Questions remained concerning other cancers, dietary assessment, quantity consumed, confounding, and differential study quality. Here we expand the review to 40 case-control studies of 20 cancers and colon polyps. Odds ratios are < 1 for 46 of 51 mentions of whole-grain intake and for 43 of 45 after exclusion of 6 mentions with design/reporting flaws or low intake. The pooled odds ratio for high vs. low whole-grain intake among the 45 mentions was 0.66 (95% confidence interval = 0.60-0.72); they range from 0.59 to 0.78 across four types of dietary questionnaires. Odds ratios were < 1 in 9 of 10 mentions of studies of colorectal cancers and polyps, 7 of 7 mentions of gastric and 6 of 6 mentions of other digestive tract cancers, 7 of 7 mentions of hormone-related cancers, 4 of 4 mentions of pancreatic cancer, and 10 of 11 mentions of 8 other cancers. Most pooled odds ratios for specific cancers were in the range of 0.5-0.8, notable exceptions being breast (0.86) and prostate (0.90). The pooled odds ratio was similar in studies that adjusted for few and many covariates. Dose-response associations were stronger in studies using food-frequency questionnaires than in more quantitative questionnaires. The case-control evidence is supportive of the hypothesis that whole-grain intake protects against various cancers.