CTX-M-15, an extended-spectrum β-lactamase emerging worldwide, hydrolyzes lactam ring of β-lactam antibiotics, and thus causes therapeutic failure and a lack of eradication of pathogenic bacteria by third-generation β-lactams. Therefore, the enzyme is a potential target for developing agents against pathogens isolated from patients suffering from nosocomial infections. The CTX-M-15 protein was purified and crystallized at 298 K. X-ray diffraction data from CTX-M-15 crystal have been collected to 1.46 Å resolution using synchrotron radiation. The crystal of CTX-M-15 belongs to space group P2(1)2(1)2(1), with unit-cell parameters a = 45.50, b = 44.23, and c = 116.92 Å. Analysis of the packing density shows that the asymmetric unit probably contains two molecules with a solvent content of 41.26%.