Therefore, in this study we identified nine patients affected with polyposis (two of them diagnosed after initiating CRC surveillance) with biallelic pathogenic or likely pathogenic NTHL1 variants belonging to three separate families (Figure 1), as well as two families with one pathogenic or likely pathogenic NTHL1 variant in concomitance with the VUS NM_002528.7:c.503T>C p.(Ile168Thr) (Figure 2). This evidence concerns the gene NTHL1 and colorectal carcinoma.