Because of the potential implications of results of genetic analyses of thrombophilic mutations, laboratories must undertake stringent internal quality control measures and participate in external quality assurance (QA) programs. A small number of external QA surveys of thrombophilic defects have been conducted across a large number of molecular laboratories and generally have indicated favorable levels of correct responses. The Royal College of Pathologists of Australasia QA program has conducted external QA testing of factor V Leiden G1691 A, prothrombin G20210A, and MTHFR C677T gene mutations for the past 5 years, including 133 DNA samples in 10 multilaboratory surveys. Of 3,799 responses, the overall success rate was 98.63%; the poorest individual sample result was 15% incorrect for a homozygous factor V Leiden sample. Success rates in identifying specific mutations were 98.13% for factor V Leiden, 98.84% for prothrombin G20210A, and 99.3% for the MTHFR C677T mutation. Among responding laboratories, 51% (20/39) made at least 1 error; 3 of 39 laboratories were responsible for 46% of all errors (24/52). Although encouraging, these data underscore the need for ongoing participation of molecular diagnostic laboratories in external QA programs to ensure the provision of quality genetic testing services.