Since the hypothesis that vitamin D reduces the risk of some cancers was initiated in 1980, this hypothesis has been studied in the Harvard cohort studies, including the Nurses' Health Study (NHS), the Health Professionals Follow-Up Study (HPFS), and the Physicians' Health Study (PHS). Three approaches have been used, the study of circulating 25(OH)vitamin D (25(OH)D) level, of dietary and supplementary intake, and of predicted 25(OH)D. These cohorts strongly support an inverse association with colorectal cancer, because this association has been viewed in both the NHS and HPFS cohorts, for cancers and adenomas, and for plasma, diet, and predicted 25(OH)D analyses. In the NHS, about a 30% reduction in risk was observed for breast cancer comparing the highest with lowest quintiles of 25(OH)D levels. Vitamin D intake also was associated with a lower risk of pancreatic cancer in both men and women, but studies of plasma or predicted 25(OH)D level or dietary intake have generally not been supportive of a major role of vitamin D status in middle-age or elderly men on prostate cancer risk. Results from the HPFS also suggest that the poor vitamin D status generally in African-Americans contributes to their higher incidence and mortality from various malignancies.