This study investigates the genetic evolution of pancreatic cancer, focusing on the timing and mechanisms of distant metastasis. By sequencing seven pancreatic cancer metastases, the researchers found that the clonal populations giving rise to these metastases are already present within the primary carcinoma but have evolved genetically from the original, non-metastatic clone. The analysis revealed that the genetic heterogeneity of metastases reflects that within the primary carcinoma. Quantitative analysis indicated a significant time window of at least a decade between the initiation of tumorigenesis and the development of metastatic lesions, with an additional five years required for the acquisition of metastatic ability. The study also highlighted the importance of early detection to prevent deaths from metastatic disease, suggesting a potential window of opportunity for diagnosis and intervention. The findings provide new insights into the genetic features underlying pancreatic cancer progression and the challenges in early detection and treatment.This study investigates the genetic evolution of pancreatic cancer, focusing on the timing and mechanisms of distant metastasis. By sequencing seven pancreatic cancer metastases, the researchers found that the clonal populations giving rise to these metastases are already present within the primary carcinoma but have evolved genetically from the original, non-metastatic clone. The analysis revealed that the genetic heterogeneity of metastases reflects that within the primary carcinoma. Quantitative analysis indicated a significant time window of at least a decade between the initiation of tumorigenesis and the development of metastatic lesions, with an additional five years required for the acquisition of metastatic ability. The study also highlighted the importance of early detection to prevent deaths from metastatic disease, suggesting a potential window of opportunity for diagnosis and intervention. The findings provide new insights into the genetic features underlying pancreatic cancer progression and the challenges in early detection and treatment.