Hemminger JA, et al. - This research investigated if histomorphology could distinguish patients with double somatic (DS) mutations from those with Lynch syndrome (LS). The enrollment consisted of colorectal cancer patients with DS mutations, selected from population-based cohorts from Iceland (2000–2009), Columbus, Ohio (1999–2005), and the state of Ohio (2013–2016). No marked variation was discovered in the histologic features between tumors in LS patients and tumors with DS mutations. Findings also displayed that tumor sequencing for evaluation of DS mutations ought to be taken into account for clarifying sporadic vs hereditary causes of unexplained mismatch repair (MMR) deficiency since histology of tumors with DS mutations was indistinguishable from those caused by LS.