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). The gene discussed is NTHL1; the disease is polyposis.