Genetic testing to assess POLE/POLD1 variants should be considered in glioma patients with a positive family history of gliomas, other brain tumors, colorectal, endometrial or breast cancer, particularly if they are affected by giant cell glioblastoma or oligodendroglioma, exhibit spinal metastasis or skin lesions, or have a positive history of colorectal adenomas or carcinomas. The gene discussed is POLE; the disease is breast cancer.