Menlo Park, California, USA, September 1, 2026
BillionToOne has launched Northstar Origin™, a new liquid biopsy add-on test designed to help physicians identify the tissue of origin in patients with cancer of unknown primary (CUP) or uncertain cancer diagnoses. The physician-ordered test analyzes circulating cell-free DNA (cfDNA) from a single blood draw and is designed to provide a molecular prediction of where a patient’s cancer originated without requiring additional tissue or a separate blood collection. The launch represents an advancement in molecular diagnostics, liquid biopsy technology and precision oncology, particularly for patients in whom conventional pathology and imaging cannot confidently establish the primary tumor site. BillionToOne announced the launch on September 1, 2026, alongside an expansion of its Northstar Select® comprehensive genomic profiling panel from 84 to 102 genes.
Northstar Origin Targets Cancer Diagnosis Challenges
Identifying the primary site of a tumor can be difficult when cancer cells are discovered after they have spread or when conventional diagnostic investigations do not provide a definitive answer. BillionToOne estimates that approximately 3% to 5% of new cancer diagnoses present as cancer of unknown primary, while uncertain diagnoses may affect an even larger proportion of patients in some community oncology settings. Limited tissue availability and variable sample quality can further complicate tissue-based investigations. Northstar Origin is designed to provide an additional molecular diagnostic signal using the blood sample already collected for Northstar Select testing, potentially reducing the need for additional tissue sampling or separate blood draws. The assay combines DNA methylation profiling with information from tissue-specific somatic variants identified through Northstar Select. By integrating these molecular signals, the supervised classifier generates predictions regarding the likely tissue from which a patient’s cancer originated. BillionToOne positions the technology as a diagnostic aid that complements pathology, imaging and the broader clinical picture, rather than as a replacement for conventional clinical evaluation. This distinction is important because tissue-of-origin prediction is intended to support clinical decision-making while physicians continue to consider pathology and other diagnostic evidence.
Validation Study Shows Tissue-of-Origin Accuracy
BillionToOne reported that the performance of Northstar Origin was evaluated using an independent validation cohort of 1,578 patients. The supervised model had previously been developed using 6,025 blood samples from patients with advanced cancer submitted to the company’s clinical laboratory. In the independent evaluation, the model identified the correct tissue of origin as its top prediction in 87% of cases, while the correct tissue was included among the top three predictions in 91% of cases. The company plans prospective studies to evaluate the test’s clinical utility further and expand the model to additional tumor types. The reported findings highlight the potential role of cfDNA-based molecular profiling in situations where determining the primary tumor location remains challenging. For community oncology practices, access to specialized pathology resources and multidisciplinary tumor boards may vary. A blood-based molecular test that can be incorporated into an existing liquid biopsy workflow could provide physicians with an additional source of information when establishing a diagnosis and considering treatment strategies.
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Northstar Select Expands to 102 Genes
Alongside the Northstar Origin launch, BillionToOne announced the expansion of Northstar Select from 84 to 102 genes. The additional 18 genes include MTAP deletion, an emerging biomarker of clinical interest, as well as a copy-number-loss biomarker that can be challenging for liquid biopsy assays to detect. Northstar Select is designed for comprehensive genomic profiling of advanced solid tumors and supports the identification of molecular alterations that may help guide therapy selection. The company has also reported comparative performance data for Northstar Select. In a prospective head-to-head study involving 182 patients across more than 17 solid tumor types, BillionToOne reported that Northstar Select detected 51% more clinically actionable or pathogenic single-nucleotide variants and insertions/deletions and 109% more copy-number variants than the aggregated comparator results, while producing 45% fewer null reports. These results form part of the company’s broader effort to increase the sensitivity and clinical utility of liquid biopsy-based genomic testing. Importantly, BillionToOne states that Northstar Origin, Northstar Select and Northstar Response are laboratory-developed tests performed in a CLIA-certified and CAP-accredited laboratory and have not been cleared or approved by the U.S. FDA. The company also emphasizes that Northstar Origin results should be interpreted alongside pathology and other clinical information. The launch nevertheless marks a significant development in precision oncology diagnostics, demonstrating how single-blood-draw molecular profiling is being expanded beyond genomic therapy selection toward tissue-of-origin prediction and more comprehensive cancer characterization.
Source: BillionToOne press release
