A University of Pittsburgh-led team reported that BiliSeq, a 28-gene next-generation sequencing panel for bile duct tissue, meaningfully improves bile duct cancer detection compared with pathology alone. In a six-year prospective real-time study across more than 2,000 patients with bile duct strictures, BiliSeq detected about 82% of cancers versus 44% with pathology alone. When paired with pathology, detection rose to nearly 90% while maintaining high specificity. The work tested updated BiliSeq versions (V2 and V3), with sensitivity and specificity evaluated against CA19-9-based measures and standard histopathology. The study’s design and performance targets position BiliSeq as a practical adjunct for clinicians who struggle to distinguish benign from malignant etiologies in bile duct obstruction workflows.