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2 Background Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis and limited therapeutic options. Mitotane is considered the standard first line therapy with only 30 % of the patients showing objective tumour response. Defining predictive factors for response is therefore of clinical importance. The Epidermal Growth Factor Receptor (EGFR) has been implicated in the development of 1/3 of all malignancies. EGFR pathway members in ACC have been investigated, however without available clinical data and relation to survival. Methods In the present study mutation status of EGFR and downstream signalling pathways was evaluated in 47 ACC patients on mitotane using direct sequencing, a TaqMan allele-specific assay and immunohistochemistry. Archival formalin-fixed paraffin-embedded tumour tissue (FFPE) was used for all analyses. Patient dat