Ocrelizumab is a humanized monoclonal anti-CD20 antibody approved for treatment of relapsing-remitting and primary progressive multiple sclerosis (MS). Before approval of this drug, the chimeric anti-CD20 antibody rituximab was used off-label for treatment of MS. On treatment with rituximab late-onset neutropenia (LON) was reported as a rare adverse event. Here we report the case of a patient with MS who first received rituximab without experiencing any hematologic abnormalities, but developed grade IV LON after switching to ocrelizumab. This first case of LON in a patient treated with different anti-CD20 antibodies highlights the necessity of regular hemogram examinations during ocrelizumab.