Medullary thyroid carcinomas (MTC) are rare neoplasms derived from the calcitonin-producing thyroid parafollicular C-cells. Interestingly about 20% of cases are related to inherited tumor syndromes. As precursor lesion, C-cell hyperplasia can be detected in numerous MTCs. In our series of 6 patients with MTC, including 5 patients with adjacent C-cell hyperplasia, Her2/neu levels were immunohistochemically evaluated on formalin-fixed, paraffin-embedded tissues using c-erbB-2/Her-2/neu Oncoprotein Ab-17 monoclonal antibody(mAb). Statistically, a highly significant correlation was found between high Her2/neu levels and extrathyroidal growth. C-cell hyperplasias always presented with higher amounts of stained cells than their corresponding invasive MTCs. Whereas in hyperplastic areas large stained cell clusters were found, the invasive tumors showed mainly single cells reacting in areas of variable size. These results present the impact of Her2/neu oncoprotein concerning development and biological behaviour, especially aggressive growth, of invasive MTCs and suggest a major role of hyperplastic C-cell areas in the development of these malignant tumors.