LFS was first discovered in 1969. By reviewing the medical records and death certificates of children with a relatively rare tumor, a soft tissue sarcoma called rhabdomyosarcoma, Drs. Fred Li and Joe Fraumeni at the National Cancer Institute identified several families in which siblings or cousins also had a childhood sarcoma. These same families had exceptional histories of breast cancer and other tumors and proved to have LFS.
The spectrum of cancers in LFS has been shown to include breast cancer, soft tissue sarcomas, brain tumors, a bone tumor called osteosarcoma, leukemia, and a tumor of the adrenal gland (adrenocortical carcinoma): an incredible range of malignancies.
The Li-Fraumeni syndrome has been found to be due to a mutation (a heritable change) in a gene that normally serves to curb cancer: the p53 tumor-suppressor gene. LFS has been of considerable importance to the understanding of the genetics and molecular biology of cancer.