Compared with CLL patients with SPEN wild type, CLL patients with SPEN mutations had a statistically higher frequency of IGHV unmutated status (79.5% vs. 57.8%, p = 0.004), CD38 positivity (73.3% vs. 52.4%, p = 0.01), ZAP70 expression (77.3% vs. 58.3%, p = 0.01), and trisomy 12 (43.5% vs. 13.7%, p < 0.001). The gene discussed is ZAP70; the disease is B-cell chronic lymphocytic leukemia.