The role of neoadjuvant chemotherapy, radiotherapy & immunotherapy in colorectal cancer is changing & has important consequences for pathology. Complete pathological response rates are increasing. Many clinicians & patients now choose on the basis of a complete clinical response to ‘watch and wait’. Long term survival is not inferior compared with surgery & approximately 70% of patients survive with organ preservation. Surgery alone remains curative in early-stage colorectal cancers. As non-operative approaches increase larger biopsies will be essential to provide optimal tissue for MMR testing & molecular testing. Universal MMR testing of CRC biopsies is now advised, however, opportunities exist to develop additional biomarkers (tumour budding, TILs & molecular). Rates of ‘salvage surgery’ are also increasing due to inevitable re-growth in a small % of patients. TRG (tumour regression grading) will need to be adapted to the neoadjuvant immunotherapy era in deficient MMR (dMMR) CRC. Finally neoadjuvant-effect in lymph nodes & liver are not routinely reported & this may need to be incorporated into routine reporting in the future.