Blacks have been documented to have low vitamin D levels. We thus examined whether total cancer incidence and mortality rates differ between Blacks and Whites in a population of male health professionals, and particularly for digestive system cancers (oral, esophagus, stomach, pancreas, and colorectum), which have been most consistently linked to poor vitamin D status. Second, we examined whether Blacks might be more susceptible to these cancers if they concurrently had other risk factors for hypovitaminosis D. In the Health Professionals Follow-up Study, from 1986 to 2002, 99 of 481 Black men and 7,019 of 43,468 White men were diagnosed with cancer. Adjusting for multiple dietary, lifestyle, and medical risk factors, using Cox modeling, Black men were at higher risk of total cancer incidence [relative risk (RR), 1.32; 95% confidence interval (95% CI), 1.08-1.61; P = 0.007] and total cancer mortality (RR, 1.89; 95% CI, 1.40-2.56; P < 0.0001) and especially digestive system cancer mortality (RR, 2.24; 95% CI, 1.35-3.70). Compared with Whites with relatively few risk factors for hypovitaminosis D, Blacks also with few risk factors for hypovitaminosis D were not at appreciably higher risk of total cancer incidence (RR, 0.95; 95% CI, 0.60-1.51) or mortality (RR, 1.55; 95% CI, 0.91-2.62), but Black men with additional risk factors for poorer vitamin D status had a much higher cancer incidence (RR, 1.57; 95% CI, 1.16-2.11) and mortality risk (RR, 2.27; 95% CI, 1.57-3.28). This pattern was even more pronounced for digestive system cancer. Our results suggest that the high frequency of hypovitaminosis D in Blacks may be an important, and easily modifiable, contributor to their higher risk of cancer incidence and mortality.