Three brothers had separate childhood cancers--osteogenic sarcoma, acute lymphoblastic leukemia, and bilateral malignant neurilemoma. Comprehensive family history showed a total of 16 cases of cancer among the descendants of the proband's great-great-great-grandmother, including a previously unsuspected cluster of similar neoplasms in an distant branch. The constellation of tumors in the family included bony and soft-tissue sarcomas, brain and neural tumors, leukemia, and breast carcinoma, occurring in a pattern suggesting the action of an incompletely penetrant autosomal dominant gene with pleiotropic effects. In some cases the genetic predisposition may have interacted with environmental determinants to produce particular tumors.