Abstract Disclosure: N. Ding: None. S.K. Majumdar: None. Background: Hypercalcemia can be seen in patients with malignancy. However, primary splenic large B cell lymphoma presenting with hypercalcemia and renal failure is rare. Clinical Case: A 75-year-old male with PMH of migraine headaches and hearing loss was sent to the hospital by his primary care doctor due to lab abnormalities, including hypercalcemia and renal failure. He also had abdominal pain, weakness, polyuria, and weight loss for several weeks. He took calcium 1000 mg and vitamin D 5000 units daily. Laboratory tests showed creatinine 2.8 (0.4-1.3) mg/dL, calcium 13.8 (8.8-10.2) mg/dL, ionized calcium 6.75 (4.6-5.08) mg/dL, phosphorus 3.6 (2.2-4.5) mg/dL, PTH 12.6 (15-65) pg/mL, PTHrP 23 (14-27) pg/mL, 25-hydroxy vitamin D 53 (30-100) ng/mL, 1,25-dihydroxy vitamin D 171 (18-72) ng/L, CTX collagen C-telopeptide 1137 pg/ml, SPEP without significant abnormality, UPEP with Bence-Jones proteinuria. Skeletal series showed no suspicious lesions, but MRI abdomen revealed an 11 cm splenic mass. Patient underwent splenectomy and pathology revealed diffuse large B-cell lymphoma. Following surgery, his hypercalcemia resolved without additional interventions. 1,25-dihydroxy vitamin D reduced to 25 ng/l and CTX reduced to 451 pg/ml. Further workup, including bone marrow biopsy and imaging, were negative. Patient was subsequently diagnosed with primary splenic large B cell lymphoma. He completed R-CHOP therapy and had no hypercalcemia in follow-up labs. Conclusion: Calcitriol-mediated hypercalcemia occurs in less than 1% of lymphomas, and primary splenic lymphoma constitutes less than 1% of non-Hodgkin lymphomas. The case represents an extremely rare etiology for hypercalcemia. Interestingly, elevated 1,25-dihydroxy vitamin D and hypercalcemia resolved after splenectomy. Clinicians should consider lymphoma as a potential cause of hypercalcemia and renal failure in elderly patients. Presentation: Friday, June 16, 2023