The present work shows that CHIP targets the newly synthesized, HSP90/HSC70-associated ErbB2 for ubiquitin/proteasome-dependent degradation in the endoplasmic reticulum and Golgi, thus identifying a novel mechanism that negatively regulates the cell surface display of overexpressed ErbB2 levels in breast cancer cells, explaining in part the frequency of CHIP expression in ErbB2-overexpressing breast cancers. The gene discussed is STUB1; the disease is breast cancer.