HER4 belongs to the epidermal growth factor (EGF) family. Mutations in HER4 are associated with malignant melanoma. This points to HER4 as an important receptor in malignant melanoma and also raises the question of whether the other receptors in the EGF system could be involved. RT-qPCR mRNA quantification was carried out of all four EGF receptors (EGFR, HER2, HER3, and HER4) and the HER4 cytoplasmic isoforms in lymph node metastases from patients with malignant melanoma. We related their expression to progression of the disease. HER4 expression was found to be an indicator of short progression-free survival (P=0.0340). Interestingly, of the two cytoplasmic splice variants of HER4, the association of CYT1 (P=0.0176) with progression-free survival was more pronounced than that for CYT2 (P=0.0458). Also, HER3 was associated with progression-free survival (P=0.0169), whereas no association was found for EGFR or HER2 with time to progression. Our results further emphasize the role of HER4 as an important oncogene in malignant melanoma and point to HER4 as a possible drug target in this disease.