Over 30 years since it was first described as a discrete clinical entity, the antiphospholipid antibody syndrome (APS) remains a challenge for both laboratory workers and clinicians in a wide range of specialties. In addition to the presence of appropriate clinical features, the diagnosis of APS also fundamentally requires the finding of positive antiphospholipid antibody (aPL) test result(s), which comprise clot-based assays for the identification of lupus anticoagulant (LA) and immunologic ("solid-phaseo") assays such as anticardiolipin antibodies (aCL) and anti-glycoprotein I antibodies (aPI). This article is the first of two that review the process for, and provides recommendations to improve, internal quality control (IQC) and external quality assurance (EQA; or proficiency testing) for aPL assays. These processes are critical for ensuring the quality of laboratory test results and thence the appropriate clinical diagnosis and management of APS. This article covers aCL and aPI testing. In brief, IQC is a process that helps control the quality of laboratory test results on a test-by-test basis; IQC should include samples that provide values around the assay critical cut-off values, and there is added value in the inclusion of non-kit assay controls. EQA is a process that helps laboratories assess their performance against those of their peers. For aCL and aPI testing, we provide some updated findings from the Royal College of Pathologists of Australasia Immunology Quality Assurance Program, and covering testing for the past 3 years (2009 to 2011 inclusive). Findings show similar trends to past years, indicating limited improvement in cross-laboratory test results and interpretations. In summary: (1) EQA participants reported greatly varying numerical test data for both aCL and aPI, with interlaboratory coefficients of variation > 50% with most test challenges; (2) there was considerable overlap in the interpretation (negative, positive, low positive, moderate positive, strong positive) that different participants ascribed to identical numerical test results; and (3) there was limited consensus among participants as to whether test results for individual EQA specimens were either positive or negative for aCL and/or aPI.