Glypican-1 (GPC1) identifies cancer exosomes and facilitates early detection of cancer. Exosomes are lipid bilayer-enclosed extracellular vesicles that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. The study identified GPC1 as a specific marker for cancer cell-derived exosomes. GPC1-positive circulating exosomes (crExos) were detected in the serum of patients with pancreas cancer with high specificity and sensitivity, distinguishing healthy subjects from cancer patients. GPC1-positive crExos correlated with tumor burden and survival in patients. GPC1-positive crExos from patients and mice with spontaneous pancreas tumors driven by oncogenic KRAS contained RNA with specific KRAS mutations, making GPC1 a reliable biomarker for detecting PanIN lesions. GPC1-positive crExos may serve as a non-invasive diagnostic and screening tool for early-stage pancreas cancer. The study also showed that GPC1-positive crExos could detect early-stage pancreatic cancer with high accuracy, outperforming CA 19-9. GPC1-positive crExos levels correlated with tumor burden in mice and could inform on metastatic disease burden in PDAC patients. GPC1-positive crExos levels decreased significantly after surgical resection, indicating their potential as a prognostic marker. GPC1-positive crExos were also found to detect early PanIN lesions in mice, even when MRI was negative. The study highlights the potential of GPC1-positive crExos as a reliable biomarker for early detection of pancreas cancer.Glypican-1 (GPC1) identifies cancer exosomes and facilitates early detection of cancer. Exosomes are lipid bilayer-enclosed extracellular vesicles that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. The study identified GPC1 as a specific marker for cancer cell-derived exosomes. GPC1-positive circulating exosomes (crExos) were detected in the serum of patients with pancreas cancer with high specificity and sensitivity, distinguishing healthy subjects from cancer patients. GPC1-positive crExos correlated with tumor burden and survival in patients. GPC1-positive crExos from patients and mice with spontaneous pancreas tumors driven by oncogenic KRAS contained RNA with specific KRAS mutations, making GPC1 a reliable biomarker for detecting PanIN lesions. GPC1-positive crExos may serve as a non-invasive diagnostic and screening tool for early-stage pancreas cancer. The study also showed that GPC1-positive crExos could detect early-stage pancreatic cancer with high accuracy, outperforming CA 19-9. GPC1-positive crExos levels correlated with tumor burden in mice and could inform on metastatic disease burden in PDAC patients. GPC1-positive crExos levels decreased significantly after surgical resection, indicating their potential as a prognostic marker. GPC1-positive crExos were also found to detect early PanIN lesions in mice, even when MRI was negative. The study highlights the potential of GPC1-positive crExos as a reliable biomarker for early detection of pancreas cancer.