A real‑world study of 888 solid‑tumor patients demonstrated clinical utility for routine paired tumor‑normal whole‑genome sequencing (WGS). The diagnostics succeeded in 89% of cases with a median turnaround of six working days and identified potentially actionable biomarkers in 73% of patients. Within a year, 40% of patients started biomarker‑informed treatments; overall, WGS-informed results had clinical consequences for 41% of tested patients and correlated with a median overall survival benefit of 96 days versus non‑biomarker‑informed care. In cancers of unknown primary, WGS contributed to diagnosis or reimbursed treatment options in 67% of cases. The data underscore WGS as a versatile, tumor‑agnostic diagnostic that can streamline biomarker detection and influence treatment selection in comprehensive cancer centers.