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Key Clinical Message  Monocytosis is often profoundly implicated in chronic myelomonocytic leukemia (CMML). We diagnosed a 63‐year‐old woman with  CMML  involving heterochronological systemic polyserositis with infiltrating benign monocytes. The patient's pleural effusion was eliminated completely with corticosteroid therapy. We speculate that our case represents an immunological reaction with activated monocytes triggered by infection.

Chronic myelomonocytic leukemia presenting with polyserositis due to an immune‐mediated monocyte activation