Li-Fraumeni syndrome (LFS) is an autosomal-dominant condition characterized by early-onset sarcoma, breast cancer and other specific tumour types. In most LFS kindreds germline TP53 mutations have been identified. In general, TP53 germline mutations are not associated with late-onset common cancers. We encountered a large kindred in which a wide spectrum of tumour types occurred, including melanoma, breast, ovarian, colorectal, stomach and renal cell cancer, without clear-cut early ages at onset of disease. An Arg213Gln TP53 germline mutation was detected in 12 out of 15 affected family members whereas testing for other cancer susceptibility genes in selected patients was negative. In vitro testing indicated that the specific TP53 mutation inactivates the protein transcriptionally. Our findings suggest that this TP53 germline mutation is a causative factor in this family and that specific TP53 germline mutations can be associated with relatively late-onset common cancers.