In their paper in this issue of the Journal, Xian et al have analysed in detail the Fallopian tubes from two patients with Li–Fraumeni syndrome (germline TP53 mutation) in order to investigate further the possible role of p53 signatures in the development of high-grade pelvic serous carcinoma. They find an increased frequency of p53 signatures, with associated evidence of DNA damage and loss of heterozygosity at the wild-type TP53 allele, but postulate, as Li–Fraumeni syndrome is not associated with an increased risk of pelvic serous carcinoma, that these events are not sufficient for the development of carcinoma. Rather, they put forward a model postulating that further events, particularly loss of BRCA1/2 function, are required for lesion progression. This paper exemplifies how the hypothesis-driven study of a rare syndrome can be highly effective at answering specific questions about disease processes. It is of note that recent evidence from the same group provides convincing evidence that the distal Fallopian tube may, in fact, be the commonest site of origin for high-grade pelvic serous carcinomas, most of which may originate at this site rather than from the ovary. In addition to its biological significance, this, if proven, has clear clinical implications. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.