The risk of a person developing a second primary cancer was evaluated in approximately 55,000 women diagnosed with breast cancer in Denmark between 1943 and 1980. Excluding second cancers of the contralateral breast, 2,480 new cancers were observed compared with 2,398 expected (relative risk = 1.03; 95% CI = 0.99-1.08). Breast cancer patients followed for 10 years or more showed a significant 13% excess of all second primary tumors. Significant excesses of cancers of the lung, bone, and connective tissue were observed. Although some misclassification of metastases may have occurred, the risk of second cancers at these sites (as well as the salivary gland and esophagus) increased significantly with time and was especially high among women followed for 10 years or more. These observations suggest that radiation, as a part of the initial treatment, may have been involved. Radiation or chemotherapy, or both, may also have influenced the risk of acute nonlymphocytic leukemia (51 cases observed vs. 20.7 expected), which remained significantly elevated after the first year of follow-up. Common risk factors, related to reproductive experience and nutrition, may have contributed to the excess risk of cancers of the ovary and colon. On the other hand, an anticipated excess of cancer of the corpus uteri was not found, although cancer of the uterus not otherwise specified was significantly increased. Significant deficits were observed for second cancers of the liver and biliary tract, due perhaps to underreporting or conservative coding practices, or both. A significant excess of malignant melanoma was not easily explained but might indicate a common hormonal etiology with breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)