Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating immunoglobulin (Ig) G antibodies that recognize multimolecular complexes of platelet factor 4 (PF4) bound to heparin or other polyanions. Most laboratory assays for HIT have a high sensitivity for anti-PF4/heparin antibodies and a negative test generally excludes HIT (high negative predictive value), especially in a setting of a low pretest probability. The magnitude of a positive test result correlates with greater likelihood of HIT. Therefore, a combined diagnostic approach that considers the clinical picture and the magnitude of a positive test result is recommended for accurate diagnosis of HIT.