Introduction: Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by the clonal proliferation and accumulation of mature monoclonal B lymphocytes in the peripheral blood. CLL is relatively common in Europe and North America, with an incidence of approximately 4–6 cases per 100,000 population, whereas it is rare in South Asia, with an incidence of approximately 0.11 cases per 100,000 population. During the course of the disease, neoplastic lymphocytes may infiltrate the bone marrow, lymph nodes, liver, spleen, and, less commonly, other organs and tissues. CLL presenting with marked splenomegaly in the absence of lymphadenopathy is uncommon. Therefore, in patients with unexplained splenomegaly, the differential diagnosis should include CLL and other lymphoproliferative disorders. Case Presentation: We report a case of CLL diagnosed on the basis of clinical findings, laboratory investigations, and additional diagnostic evaluation in a patient who presented to a hematology outpatient clinic with splenomegaly. An 81-year-old man presented with a macular rash involving the thighs, lower legs, chest, and both upper extremities, accompanied by dizziness, unsteadiness, nausea, fatigue, and generalized weakness. Physical examination revealed massive splenomegaly with a smooth surface and blunt edge, palpable approximately 25 cm below the left costal margin. Laboratory investigations demonstrated hyperleukocytosis with lymphocytosis, moderate normocytic normochromic anemia, and severe thrombocytopenia. Contrast-enhanced abdominal computed tomography revealed massive splenomegaly, with the spleen measuring 27.9×20.0×7.9 cm. The patient was treated with cyclophosphamide at a dose of 250 mg/m (400 mg administered) in combination with glucocorticoid therapy. Following treatment, leukocytosis, lymphocytosis, and monocytosis improved, and the spleen decreased substantially in size, becoming palpable approximately 4 cm below the umbilicus on physical examination. Conclusion Hematologic malignancies should be considered in the differential diagnosis of patients presenting with unexplained splenomegaly. In this case, a diagnosis of chronic lymphocytic leukemia was established based on bone marrow examination and the overall clinical and laboratory findings. Following treatment with cyclophosphamide and glucocorticoids, peripheral blood abnormalities improved and splenic enlargement decreased substantially, suggesting a favorable therapeutic response.