Background: Thyroxine protein binding abnormalities are a rare cause of discordant thyroid function tests in otherwise clinically euthyroid individuals. We report a mother and daughter pair with Familial Dysalbuminaemic Hyperthyroxinaemia causing inappropriately high free T4 levels as measured by immunoassay. Case report: A 69 year old female was referred to the thyroid clinic for assessment of discordant thyroid function tests. Biochemistry dating back to July 2015 showed persistently elevated free T4 levels by immunoassay ranging between 25 pmol/L to 34 pmol/L with normal or slightly decreased TSH values ranging between 0.05 mU/L to 1.90 mU/L. The patient was taking thyroxine for Hashimoto’s thyroiditis and had been on a stable dose of 100 mcg daily for the past 30 years without any symptoms suggestive of thyrotoxicosis. Previously, dosage reduction of thyroxine to 75 mcg daily resulted in symptoms of hypothyroidism. Measurement of free T4 using Liquid Chromatography - Tandem Mass Spectrometry (LCMS/MS) gave a value of 19.5 pmol/L. Exome sequencing (confirmed by Sanger sequencing) detected a guanine to adenine substitution at residue 725 in exon 7 of the ALB gene, which predicts an arginine to histidine amino acid change (NM_000477; exon7; hg38: c.G725A:p.R242H). This variant has previously been reported as associated with dysalbuminaemic hyperthyroxinaemia, and is classified as pathogenic. Subsequent testing of the patient’s daughter revealed a similar pattern of thyroid function tests on immunoassay and LCMS/MS as well as the same genetic variant. Comparison of results obtained by different free T4 assays showed the Roche and Centaur platforms to be most affected by the variant, whereas the Abbott Architect gave the best agreement with LCMS/MS. Conclusion: Familial Dysalbuminaemic Hyperthyroxinaemia can result in elevated free T4 levels on immunoassay methods and should be considered in the differential diagnosis of discordant thyroid function tests.