Abstract Disclosure: S. Lamichhane: None. D.T. Price: None. J.J. Faria-Briceno: None. A. Kaur: None. Introduction: Paragangliomas are rare neuroendocrine tumors comprising about 15-20% of all chromaffin cell tumors and can arise anywhere along the sympathetic and parasympathetic ganglionic chain from skull base to the pelvic floor. About 75% of sympathetic paragangliomas arise in the abdomen out of which majority are functional and secrete catecholamines responsible for the typical clinical features. While the diagnosis is usually made by clinical features and lab elevation of catecholamines, it is estimated that 10-15% of paragangliomas are non-functional and another 10% do not manifest clinically according to the hormone activity, thus posing a significant diagnostic challenge. We report a case of a retroperitoneal paraganglioma diagnosed by biopsy as it was initially missed owing to its silent nature clinically and biochemically. Case report:A 48-year-old smoker with panic disorder, remote history of spontaneous pneumothorax, and exploratory laparotomy for motor vehicle accident visited ER due to left-sided abdominal fullness and weight loss of 10-20 pounds for several months. Review of systems was negative except for mild constipation. He denied taking any medications and BP had been normal. CT abdomen showed a large 13.3 cm mixed cystic and solid mesenteric mass. Core biopsy revealed pheochromocytoma and patient was referred to Endocrinology. Labs showed elevated plasma free metanephrines (MN) 80 pg/ml, normetanephrines (NMN) 190 pg/ml, total MN 270 pg/ml, all less than twice the upper limit of normal and inconclusive, non-elevated 24-hour urine MN and NMN but with inadequate collection, and normal plasma catecholamines. MRI revealed a 13.5 cm mass in the left retroperitoneal sympathetic chain separate from the left adrenal gland and inferior to the left kidney. After pre-op optimization with alpha and beta blocker, patient had an uncomplicated open resection of the mass along with the retroperitoneal lymph nodes (LN). Pathology resulted in 3 benign LNs, a 16.5 cm paraganglioma negative for margin, lymph-vascular invasion, and necrosis. Genetic panel was negative. Follow-up post-surgery at 1 and 3 months with mildly elevated catecholamines and MRI abdomen at 3 months without evidence of recurrent or residual mass and metastasis. PET scan is pending prior authorization. Conclusion: Silent retroperitoneal paragangliomas are exceedingly rare. The diagnosis is often missed when the tumors are asymptomatic, and biomarkers are not elevated. The lack of specific imaging characteristics also adds to the diagnostic challenge. Early recognition can avoid the potential risk of life-threatening hypertensive crisis during surgical intervention. Our case highlights the importance of considering this rare entity in the differential diagnosis of retroperitoneal mass. Presentation: 6/1/2024