Targeted DNA sequencing was performed using a custom Cancer Hotspot Panel covering recurrently mutated regions in cancer-associated genes. Genomic DNA (15 ng input) was isolated from metastatic cutaneous squamous cell carcinoma (cSCC), matched metastases, and non-metastatic (control) cSCCs skin samples.Panel based DNA sequencing provided supportive evidence to pathologist determined classification of metastatic to non-metastatic (control) lesions. Libraries were prepared using PCR-based amplicon enrichment and sequenced to identify somatic mutations and copy number alterations. Variant allele frequency thresholds were adjusted per sample based on sequencing quality metrics.