Pinol et al (2005) performed only IHC and MSI analyses among unselected CRC patients to identify MSH2 and MLH1 germline mutation carriers, whereas we also included molecular analyses for the detection of mutations of MSH6 and PMS2. Many studies have used highly selected groups of CRC patients, or included patients from hereditary cancer clinics (Young et al, 2001; Hitchins et al, 2007) Differences in study design will typically complicate comparisons with the results of population studies. The gene discussed is MLH1; the disease is colorectal carcinoma.