Although our study confirms that biallelic NTHL1 pathogenic variant carriers have a multi-tumor phenotype syndrome, we saw no evidence that the association of multiple cancers, including CRC and BC, in the absence of polyposis, should prompt genetic testing of NTHL1, since none of the 239 patients selected using this criterion presented NTHL1 pathogenic biallelic variants. This evidence concerns the gene NTHL1 and polyposis.