Disclosed herein are methods of treating diseases that exhibit over-activation of the ERBB4 pathway, such as breast cancer and lung cancer. The method comprises administering to a subject having a disease that exhibits over-activation of the ERBB4 pathway and a gene expression profile consistent with an ERBB4-sensitive profile a therapeutically effective amount of an ERBB4 inhibitor, wherein the disease is effectively treated. Gene expression profiles of ERBB4-sensitive cells and microarrays suitable for protein-tyrosine kinases are also provided.