A familial cancer aggregation comprising sarcomas, brain tumors, leukemias, and carcinomas of breast, larynx, lung, adrenal cortex, and other sites has been studied from a pathologic-genetic standpoint. Based upon sibships segregating for cancer, the genetic segregation parameter is estimated to be 45.6 f 11% which is compatible with that expected for a rare deleterious autosomal gene showing complete dominance. Pathologic review of 16 tumors by bright field microscopy revealed variable occurrences of intranuclear cytoplasmic in-vaginations, intranucleolar bodies, and acidophilic intracytoplasmic inclusions in eight lesions. Two tumors showed both intranuclear cytoplasmic in-vaginations and intranucleolar inclusions. Morphological findings coupled with the observed pattern and distribution of cancer in the subject kindred suggest that the cancer-prone genotype interacts with one or more exogenous factors in causing this familial tumor association.