ATM plays a crucial role in repairing DNA damage and maintaining genomic stability. Mutations in ATM are associated with increased breast cancer risk and the development of various neuroendocrine carcinomas, including small-cell lung carcinoma and neuroendocrine tumors of the gastrointestinal tract. Here, we present a case with a heterozygous ATM variant [(NM_000051.4.7174C>T(p.Arg2392Trp)], which is classified as a variant of uncertain significance (VUS) in the ClinVar database. This patient, who was initially treated for breast cancer, was later diagnosed with a rare vaginal neuroendocrine carcinoma at month 31 post-breast cancer diagnosis. In contrast to most cases, the patient tested negative for human papillomavirus (HPV) DNA. Based on the rare presentation of neuroendocrine carcinoma and the negative HPV DNA status, we proposed that VUS of ATM may be associated with cancer development and has pathogenic roles.