The opportunities provided by the NCI intramural program allowed us to carry out a long-term prospective study that characterized the subsequent risk of cancer in 24 families that we assembled with this dominantly inherited, devastating syndrome. It featured sarcomas of soft tissue and bone, breast cancer, brain tumors, leukemia and adrenocortical tumors, with several other cancers appearing to arise at lower levels of relative risk. The family members were also prone to multiple primary tumors, including a predisposition to sarcomas following radiotherapy. Biospecimens were collected in a search for an underlying mechanism that might explain this wide range of tumors. But we came up empty-handed until 20 years after the original report when Stephen Friend at Harvard and Esther Chang at the Uniformed Services University across the street independently detected germline mutations of the tumor suppressor gene, p53, in our families. The gene was a candidate for study since somatic mutations had recently been identified in about 50% of all cancer, including each of the tumors that we were seeing in the syndrome.