We previously identified a novel microtubule-destabilizing motif in CPAP that can disassemble microtubules. To examine further the CPAP function in human cells, we used siRNA to knockdown its expression. Our results showed that CPAP depletion arrested cells in mitosis and induced apoptosis. Interestingly, more than 40% of these mitotic cells had multiple spindle poles. Furthermore, inhibition of the kinesin Eg5 in CPAP-depleted cells resulted in monopolar spindles, indicating that Eg5 function is required for multipolar spindle formation in the absence of CPAP. Together, our results reveal a structural role for CPAP to maintain centrosome integrity and normal spindle morphology during cell division.