This study aimed to describe and molecularly characterize a rare case of early-onset multiple primary tumors associated with a novel germline <i>protection of telomeres 1</i> (<i>POT1</i>) gene pathogenic variant, associated with POT1 tumor predisposition syndrome (POT1-TPD), a rare autosomal dominant disorder characterized by an increased risk for various tumors, including gliomas. Here, POT1 is linked to BAP1-related tumor predisposition syndrome.