Lung cancer is the most lethal neoplasm worldwide, with most patients diagnosed at advanced stages, and without cure attempt possibilities throughout a therapy. Recently, activating mutations have been described as related to epidermal growth factor pathway, which are susceptible of being treated with tyrosine kinase inhibitors from epidermal growth factor receptor. As a drug class, tyrosine kinase inhibitor relates to adverse dermatological effects (acneform eruption, pruritus, skin xerosis, etc.). As an epidermal growth factor receptor tyrosine kinase inhibitor, afatinib has portrayed capability for HER2 and HER4 inhibition. Thus, it is a fact that it shares similar toxicities with other epidermal growth factor receptor tyrosine kinase inhibitors and provokes particular adverse events such as an increase in diarrhea. We report the case of a non-small cells lung cancer male patient treated at third line with afatinib and who has shown an unusual dermatological adverse effect characterized by hyperkeratosis at a subcutaneous trauma site. It is the first case reported in literature as far as we know.