ABSTRACT Background An 8.8‐year‐old male neutered Persian cat was presented with a history of recent intermittent mild lethargy, hyporexia, and weight loss. Physical examination revealed pale mucous membranes, an enlarged right mandibular lymph node, and organomegaly suspected to be an enlarged spleen. A CBC showed an extreme leukocytosis composed almost exclusively of small lymphocytes and a moderate, microcytic, slightly regenerative anemia. Objectives We aimed to diagnose the cause of the extreme leukocytosis, to classify the circulating leukocytes, and to determine the response to therapy. Methods Blood film review, biochemical and iron analysis, abdominal ultrasound, flow cytometric evaluation of leukocytes, serum and urine protein electrophoresis, and polymerase chain reaction for antigen receptor rearrangement (PARR) were performed. Results Leukocytes were mostly small lymphocytes with scant pale basophilic cytoplasm, and round or convoluted nuclei with coarse to finely clumped chromatin. There was hyperglobulinemia and iron deficiency. Imaging showed splenomegaly and multiple enlarged abdominal lymph nodes. On flow cytometry, the lymphocytes were positive for CD18, CD21, and MHC II, consistent with B‐cell lymphocytic leukemia. The cat had mild hyperglobulinemia and 2+ proteinuria, and serum electrophoresis results were interpreted as a polyclonal gammopathy. PARR showed clonal rearrangement of IGH2 and IGH3 loci. Treatment with oral prednisolone and chlorambucil resulted in resolution of the clinical signs and reduction in the leukocytosis. Conclusions B‐cell chronic lymphocytic leukemia (B‐CLL) was diagnosed, which in cats is much less frequent than T‐CLL. There was a favorable response to alkylating therapy, and the cat survived for 19 months.