A new class of fragile sites termed common fragile sites is induced by aphidicolin, an inhibitor of DNA polymerase alpha. Analysis of these common fragile sites and cancer chromosome breakpoints indicates that eight fragile sites are in bands with cancer breakpoints. This is unlikely to be due to chance (p less than 0.01). Common fragile sites are in both bands where breaks occur in carcinoma of the lung and in carcinoma of the ovary. Common fragile sites are in bands with breaks leading to constitutional chromosome abnormalities associated with cancer: hereditary renal cell carcinoma and aniridia-Wilms' tumor complex. Common fragile sites, thus, may predispose to chromosome breaks and rearrangements in cancer.