The ERBB4 (a.k.a. HER4) gene encodes a transmembrane glycoprotein acting as a cellular growth factor receptor. It belongs to the epidermal growth factor receptor subgroup of the receptor tyrosine kinase superfamily also including ERBB1 (EGFR), ERBB2, which is known to be affected by gene amplifications in a number of malignant tumors, and ERBB3. Although EGFR and ERBB2 have been shown to represent good predictive markers and appropriate targets for therapeutic approaches, relatively less is known of comparable significance for ERBB3 and ERBB4. However, there is growing evidence that cooperation of all four members of the ERBB gene family contributes to a more aggressive tumor phenotype and influences therapeutic response. Accordingly, it is assumed that the assessment of the combined amplification status of ERBB1 to ERBB4 may improve the diagnostic value significantly. Recently it was shown in a retrospective study that responsiveness to Herceptin turned out to be more efficient if tumor cells show ERBB4 gene amplification.