Abstract Disclosure: F.L. Thelmo: None. J. Watari: None. J.L. Miller: None. Thyroglobulin (TG) remains a clinical mainstay for monitoring of disease burden and recurrence in patients with differentiated thyroid cancer. TG levels are expected to be low to undetectable in patients who undergo total thyroidectomy and less than 30 ng/mL in patients who undergo thyroid lobectomy. We describe a case of a 52-year-old patient who underwent thyroid lobectomy for a 16 mm minimally invasive follicular thyroid carcinoma (single vessel angioinvasion) who was later found to have a TG level in excess of 2,000 despite no signs of metastatic disease. A 52-year-old male with past medical history of prediabetes and minimally invasive follicular thyroid cancer presented for follow-up after right lobectomy five years prior. The patient was lost to follow-up after his lobectomy. During work-up of paresthesias, a cervical spine MRI incidentally noted a 41 mm enhancing mass in the left thyroid lobe. The patient had a TSH of 1.1 mIU/L. A dedicated thyroid ultrasound was performed which found a left 2.9 cm TI-RADS 3 nodule which was biopsied and found to be benign (Bethesda II). TG level was obtained and found to be significantly elevated at 2,479.9 ng/mL with negative thyroglobulin antibodies. This was repeated twice with subsequent levels being 1,857.5 ng/mL and 2,555.1 ng/mL. TG antibodies remained undetectable throughout the clinical course. The patient had a CT chest, abdomen, and pelvis exam for which no signs of metastatic disease were detected. A skeletal survey was performed which showed no evidence of metastatic disease. The patient elected for a completion thyroidectomy to ensure there was no undetected malignancy. The patient underwent successful completion thyroidectomy. Surgical pathology showed benign nodular hyperplasia. The patient was started on replacement levothyroxine and one month later the TG level became undetectable. We would like to draw attention to this patient’s profoundly high TG levels which are normally associated with recurrence of thyroid malignancy or large goiter. After comprehensive evaluation this patient was found to have no underlying disease recurrence. A completion thyroidectomy showed no malignancy within remnant thyroid tissue or adjacent lymph nodes and repeat TG level was undetectable after completion showing that native thyroid tissue had significantly high TG production without underlying disease. We believe his remaining relatively normal thyroid lobe was a super producer of thyroglobulin. Despite TG being a sensitive marker for residual thyroid tissue and disease, the standard cut-off for lobectomy must be used with caution and may not apply to every patient. Presentation Date: Saturday, June 17, 2023