Mueller-Koch et al in describe clinical and molecular evidence for a “new entity” of hereditary colorectal cancer (CRC).¹ Clustering of CRC within families has been known for some time² and it is not surprising that some such families will meet the Amsterdam criteria (AC) even though they do not carry a germline mutation in a DNA mismatch repair gene. It has been demonstrated previously that AC positive families without evidence of a DNA mismatch repair defect do not show either the clinical or pathological features of the hereditary non-polyposis colorectal cancer/Lynch syndrome.³ With respect to CRC, differences extend to multiplicity, anatomical site, histopathology, and DNA ploidy status.³ With respect to colorectal adenomas, these are more frequent but less advanced in AC positive families in which there is no evidence of a DNA mismatch repair defect.⁴ More recently it has been shown that the differences extend to the risks of developing both CRC and extracolonic cancer.⁵ The fundamental issue is whether it is reasonable to continue to use the limited set of clinical features that comprise the AC as a diagnostic label when there is clear evidence that families that meet the AC are clinically heterogeneous.⁶