In this series, biallelic somatic alterations in MLH1 (a somatic missense variant and LOH) were found in a CRC with isolated PMS2 deficiency and neither germline nor somatic variants in PMS2. These findings suggest an alternate mechanism of PMS2 protein degradation mediated by MLH1 dysfunction rather than MLH1 loss. The gene discussed is PMS2; the disease is colorectal carcinoma.