Two probands harbored two P/LP variants in multiple CPGs. One individual with colorectal adenocarcinoma at age 50 years and breast cancer at 57 years carried a PMS2 frameshift variant (c.741−742insTGAAG [p.Pro247_Ser248fs] [Ensembl: ENST00000265849; GenBank: NM_000535.6]) and a BMPR1A nonsense variant (c.730C>T [p.Arg244∗] [Ensembl: ENST00000372037; GenBank: NM_004329.2]). Immunohistochemistry of the bowel tumor showed loss of PMS2; MSI was also demonstrated, leading to diagnostic sequencing of PMS2, although there was no family history of neoplasia other than an ovarian cancer in a second-degree relative after age 70 years. The proband had previously undergone surveillance colonoscopy for inflammatory bowel disease, resulting in the identification of a number of polyps; however, there was no evidence from histology reports that these were juvenile polyps. Additionally, an individual with bilateral pheochromocytoma at ages 16 and 35 years and no reported family history of neoplasia was identified with variants in FH (c.521C>G [p.Pro174Arg] [Ensembl: ENST00000366560; GenBank: NM_000143.3]) and MAX (c.1A>G [p.Met1Val] [Ensembl: ENST00000358664; GenBank: NM_002382.4]).29 The latter variant is predicted to abolish the MAX initiation codon, and previous analysis of tumor tissue from an individual carrying it demonstrated loss of the wild-type allele and a lack of full-length MAX protein product.30