Abstract Thyroid hormones and thyroid-stimulating hormone (TSH) laboratory tests are widely utilized worldwide, and their results have a significant impact on treatment decisions and subsequent diagnostic processes. In order to avoid misdiagnosis and inappropriate therapy, any differences between symptoms and laboratory findings should be thoroughly investigated. Many factors can cause discrepancies between thyroid function test and the patients’ clinical picture such as physiological changes, severe illness, drugs, or laboratory interference. Thyroid hormone autoantibodies, anti-streptavidin, and anti-ruthenium antibodies are the major thyroid function test interferers. Here, we present a case of a 70-year-old woman who is known to have hashimoto's thyroiditis maintained on Levothyroxine (LT4) for more than 10 years, but was stopped by her primary care physician due to abnormal thyroid panel results (high TSH and high fT4). She was referred to the endocrinology clinic for further evaluation. The patient complained of generalized fatigue and weakness. She had no hyperthyroid symptoms. She was not on any supplements. Testing thyroid hormones with the 2-step assay revealed severe hypothyroidism, so LT4 was resumed, and patient symptoms improved. This case aims to direct clinicians’ attention to the importance of considering the patient's clinical status in the diagnostic process and not replacing it with the laboratory diagnosis, given the possibility of many laboratories’ interference. Also, to underline the available methods to minimize false results and misleading diagnoses to avoid unnecessary investigations and interventions. Presentation: No date and time listed