Although MPNSTs co-express erbB3 and erbB4, our demonstration that Erbb4 ablation decreased proliferation, survival and angiogenesis in MPNSTs indicates that these receptors are not functionally redundant and suggest that erbB4 activates distinct signaling cascades essential for MPNST tumorigenesis. Here, ERBB4 is linked to malignant peripheral nerve sheath tumor.