WHAT IS ALREADY KNOWN ON THIS TOPIC Mismatch repair deficiency (dMMR), with evidence of microsatellite instability (MSI), is a hallmark of cancers occurring due to Lynch syndrome. Clear pathways exist for investigation of dMMR endometrial/colorectal cancers, but guidance for onward investigations for patients with non-colorectal/non-endometrial dMMR cancers has, to date, been limited. This study synthesises available evidence to define tumour-specific and tumour-agnostic pathways for MLH1 promoter methylation testing, germline genetic testing and selective somatic MMR gene testing. We identify tumour types where diagnostic yield justifies upfront germline testing and clarify where methylation triage can be used to direct germline analysis, providing the first UK consensus for MSI/dMMR cancers beyond colorectal and endometrial primaries. These recommendations offer a pragmatic national framework that prioritises patients with the highest likelihood of Lynch syndrome while reducing low-yield testing. This framework will support…