To determine whether there might be a statistically significant association between fragile sites and cancer breakpoints, we examined the locations of the 21 fragile sites and the 50 cancer breakpoints recently accepted by the Seventh Human Gene Mapping Workshop. Nine of the 21 fragile sites appeared to be located at or near a cancer breakpoint. The chi-square test for association gives a value of 15.8 (p less than 0.001) indicating that there is a very highly significant statistical association between human fragile sites and cancer breakpoints. This association is not narrowly limited to one class of fragile site, such as those sensitive to folate or to one type of cancer, but appears to extend to leukemia, lymphoma, and solid cancer. To more fully understand the meaning of this intriguing association between fragile sites and cancer breakpoints, future research will need to locate additional fragile sites and cancer breakpoints with precision, record their concurrence in individuals and families, determine if fragile site families are predisposed to cancer, and prove that a fragile site and a cancer breakpoint that appear to be coincident are at the same point on the DNA level.