In my commentary (Gut 2006;55:759–61), that accompanied Jover et al’s paper (Gut 2006;55:848–55), we indicated several important issues regarding colon cancer microsatellite instability-high (MSI-H) and the influence of fluorouracil-based (FU) chemotherapy on patient survival that Iacopetta and Watanabe (Gut 2006:55:1671–2) raise in their letter, some of which need to be clarified. Most important is the separation of improved survival due to a patient’s tumour microsatellite instability status from improved survival due to FU treatment. A comparison of patients with MSI-H colon tumours who received chemotherapy and patients with MSI-H tumours who did not receive chemotherapy is the only way to separate out the influence of FU on survival in this group. This is because patients with MSI-H tumours already have an improved survival over those with microsatellite …