Non-small cell lung cancers present a 5-year survival rate below 12%. Such a poor prognosis may be explained by non small cell lung cancer cells evasion to apoptosis and resistance to treatments. Amphiregulin, an epidermal growth factor-related growth factor is secreted by non-small cell lung cancer cells in an autocrine/paracrine manner to promote autonomous growth of tumor cells and to provide resistance to apoptosis. Furthermore, amphiregulin is involved in non-small cell lung cancers resistance to epidermal growth factor receptor targeted therapy. This editorial underlines the increasing role of amphiregulin in non-small cell lung cancer cells resistance mechanisms and suggests the use of amphiregulin as a marker for drug sensitivity and/or as a prognostic marker to identify patients that may respond to epidermal growth factor receptor-tyrosine kinase inhibitors.