Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) effective in non- small cell lung cancer (NSCLC) with EGFR mutations. Since the drug is primally eliminated by the fecal route no dose adjustment is needed in patient with chronic-kidney disease (CKD); despite this there is limited data about its safety in cancer patients with end-stage renal disease (ESRD). Herein, we reported a case report of a 77-year-old woman, diagnosed in 2018 with lung adenocarcinoma EGFR mutated with lymph nodal and cerebral metastasis, who started Osimertinib 80 mg/day. She under- went 41 cycles of therapy with no Osimertinib interruptions, no severe toxicities and obtaining complete radiological response. We conclude that Osimertinib has an acceptable safety profile also in cancer patients with ESRD not undergoing hemodialysis (HD).