The evaluation of leukocytosis

Leukocytosis, defined as an elevated white blood cell count, is a frequently encountered laboratory finding with a broad differential diagnosis ranging from transient reactive processes to life-threatening hematologic malignancies. Distinct patterns of elevation can provide valuable diagnostic clues that narrow the differential diagnosis and guide next steps. This article outlines a systematic approach to evaluating leukocytosis, emphasizing integration of clinical history, physical examination, and laboratory data. The discussion highlights both nonmalignant and malignant causes, including acute and chronic leukemias, lymphomas, and myeloproliferative disorders, and offers guidance on when to pursue advanced diagnostics. Finally, a practical evaluation algorithm is included to support clinical decision-making. By recognizing key clinical features, laboratory patterns, and risk factors associated with malignancy, clinicians can appropriately triage patients for specialist referral and ensure timely intervention.