The report by Aldred Scott Warthin in 1913 of a cancer family history and expanded on by Henry T. Lynch demonstrated one of the most enduring traits observed in patients with Lynch syndrome. The recognition of a variety of malignancies occurring at differing ages within a single family suggested the role of genetic variance on disease expression in an autosomal dominantly inherited genetic condition. With the identification of the genetic basis of Lynch syndrome and the subsequent collection of families and their medical records it has become possible to identify subtle genetic effects that influence the age at which disease onset occurs in this cancer predisposition. Knowledge about genetic modifiers influencing disease expression has the potential to be used to personalise prophylactic screening measures to maximise the benefits for family members and their carers.