Human epidermal growth factor receptor 2 (HER2) isoform switches from epitope‐positive to epitope‐negative splicing variants elicited resistance to the anti‐HER2 mAb trastuzumab in breast cancer patients, while CD19 and CD22 isoform switches into epitope‐negative splicing variants, and CD22 isoform switch into a noncoding splicing variant, caused resistance to CAR‐T cells in B‐lymphoid malignancies.1, 2. The gene discussed is CD22; the disease is breast cancer.