Heparin induced thrombocytopenia (HIT) is a life-threatening disorder which diagnosis depends on laboratory evaluation. The objective of this report is to present the impact of different laboratory methods for HIT detection on the diagnostic evaluation process. In this case, a 78-year old female patient previously diagnosed with monoclonal gammopathy of undetermined significance (MGUS) was administered with heparin for pulmonary embolism treatment. Patient's initial diagnostic work-up (determination of platelet count and prothrombin time measurement for monitoring of pharmacotherapy) was followed by the clinical estimation of HIT likelihood by "4Ts" score, two immunoassays (ID-PaGIA Heparin/PF4 Antibody Test and ELISA PF4 IgG assay) and one functional test called high-performance liquid chromatography serotonin release assay (HPLC-SRA). The result of "4Ts" score indicated a low likelihood of HIT but persistent thrombocytopenia that appeared days after discontinuation of heparin therapy suggested delayed-onset HIT. Both immunoassays were positive for presence of HIT-autoantibodies, while the functional HPLC-SRA was negative. Since different methods gave opposing results, their interpretation required great attention. In comparison to the HPLC-SRA, immunoassays are prone to the analytical interferences associated with the presence of non-specific antibodies, which may lead to false positive results. In this case, where the patient is known to produce antibodies of undetermined significance, HIT was ruled out as the possible cause of persistent thrombocytopenia primarily due to the negative result of HPLC-SRA, which is not prone to this type of interferences, but also due to the low "4Ts" clinical score.