Targeting epidermal growth factor receptor (EGFR)-mediated signalling pathways has become routine practice in the treatment of lung cancer. Erlotinib is an oral EGFR tyrosine kinase inhibitor, licensed for maintenance monotherapy treatment in patients with locally advanced or metastatic non-small cell lung cancer after first-line chemotherapy. The authors present the case of a 51-year-old patient who had an excellent response to erlotinib, but developed unilateral onycholysis as an unusual side effect. The authors discuss erlotinib-induced skin and nail changes and have provided a brief literature review on the available evidence for their management.