Cold agglutinin syndrome is a form of acquired hemolytic anemia that typically arises from underlying conditions, such as infections, autoimmune disorders or lymphoid malignancies. The majority of patients remain asymptomatic and are diagnosed with anemia through routine complete blood count (CBC) testing. The present study describes the case of a male patient in his 50s who sought a second opinion at the authors' clinic due to newly detected anemia. A peripheral blood smear revealed red blood cell (RBC) agglutination, and testing confirmed the presence of cold agglutinin antibodies. Thoracoabdominal computed tomography identified a mass in the right kidney, leading to a partial nephrectomy. A pathological examination of the mass confirmed a diagnosis of renal cell carcinoma. At that time, no secondary cause for the cold agglutinin syndrome was identified. At 2 years following his initial admission, the patient presented with bilaterally enlarging masses in the groin. A biopsy was performed, which revealed low‑grade B‑cell lymphoma. Following R‑CHOP treatment, the RBC agglutination was resolved, and the CBC returned to normal ranges. On the whole, the present study demonstrates that cold agglutinin syndrome may serve as an early indicator of lymphoma.

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