Aims: A subset of papillary thyroid carcinomas (PTC) is biologically aggressive leading to distant metastases, anaplastic transformation, and death. We aim to identify and validate genomic biomarkers for this subset of tumors beyond known driver mutations. Methodology: We performed integrated multi-omic profiling of a cohort of 109 PTC patients with long-term follow-up (median 14 years), including whole-exome sequencing, whole-genome sequencing, bulk RNA sequencing, and single-nucleus RNA sequencing. Tumors were stratified into risk groups based on clinical outcomes. Copy number alterations were identified using allele-specific methods. Survival analyses were performed using multivariable Cox regression models. Results: We identified a recurrent copy number signature significantly enriched in high-risk PTC and associated with development of distant of metastases, anaplastic transformation, shorter progression-free and disease-specific survival. This signature was validated across 4 independent cohorts and demonstrated increasing frequency from primary tumors to metastatic disease. Multivariable analyses confirmed its independent prognostic value beyond tumor stage and TERT promoter mutation status. Evolutionary modeling revealed that components of this signature arise early in tumor development, preceding other genomic events. Transcriptomic integration demonstrated that this signature is associated with coordinated dysregulation of cancer-relevant pathways and defines tumors with distinct molecular phenotypes. Network analyses further identified key cancer-associated and potentially targetable genes within the affected regions. Conclusion: A prognostic copy number signature identifies high-risk PTCs and provides independent risk stratification beyond established genomic and clinicopathologic markers. These findings support incorporation of copy number profiling into clinical risk assessment at diagnosis and highlight potential therapeutic vulnerabilities.