A chimeric antibody targeting CD20, rituximab is the first monoclonal antibody approved in cancer treatment, and is currently used in practically all B cell malignancies. Expression of CD20 is limited to mature and precursor B cells, and the histological demonstration of its presence in a tumour warrants the inclusion of rituximab in its therapy. However, repeated administration of rituximab can lead to the disappearance of CD20 molecule expression at B cell surface, rendering the drug useless. We here present a case of follicular lymphoma showing CD20 expression loss at relapse, emphasizing the importance of re-biopsy at relapse/progression.