This study investigates age-related hematopoietic clonal expansion and the presence of leukemia/lymphoma-associated mutations in blood samples from 2,728 individuals without apparent hematological malignancies. The researchers identified 77 blood-specific mutations in 19 genes, most of which are associated with advanced age. Notably, 83% of these mutations were found in 19 genes linked to hematological malignancies, including *DNMT3A*, *TET2*, *JAK2*, *ASXL1*, *TP53*, *GNAS*, *PPM1D*, *BCORL1*, and *SF3B1*. The frequency of these mutations increased with age, reaching 6.1% in individuals over 70 years old. The study also identified 14 additional low-level recurrent mutations in a small fraction of blood cells, suggesting early stages of clonal expansion. These findings highlight the potential role of these mutations in the development of hematological malignancies and the need for caution when using blood as a reference for germline genome analysis, especially in older individuals.This study investigates age-related hematopoietic clonal expansion and the presence of leukemia/lymphoma-associated mutations in blood samples from 2,728 individuals without apparent hematological malignancies. The researchers identified 77 blood-specific mutations in 19 genes, most of which are associated with advanced age. Notably, 83% of these mutations were found in 19 genes linked to hematological malignancies, including *DNMT3A*, *TET2*, *JAK2*, *ASXL1*, *TP53*, *GNAS*, *PPM1D*, *BCORL1*, and *SF3B1*. The frequency of these mutations increased with age, reaching 6.1% in individuals over 70 years old. The study also identified 14 additional low-level recurrent mutations in a small fraction of blood cells, suggesting early stages of clonal expansion. These findings highlight the potential role of these mutations in the development of hematological malignancies and the need for caution when using blood as a reference for germline genome analysis, especially in older individuals.