Between November 2012 and July 2014, in accordance with national law 648/96, brentuximab vedotin was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma outside a clinical trial context. A large Italian observational retrospective study was conducted on the use of brentuximab vedotin in everyday clinical practice to check whether clinical trial results are confirmed in a real-life context. The primary endpoint of this study was best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and safety profile. A total of 40 heavily pretreated patients were enrolled. Best response was observed after a median of four cycles in 77.5%: globally, 47.5% patients obtained a complete response, 64.2% in the elderly subset. The overall response rate was 62.5%. At the latest follow up, 15/18 patients are still in complete remission (3 with consolidation). The progression-free survival rate at 24 months was 39.1% and the disease-free survival rate at the same time was 54% (median not reached). All the long-term responders were aged <30 years at first infusion. The treatment was well tolerated even in this real-life context and no deaths were linked to drug toxicity. Brentuximab vedotin induces clinical responses quite rapidly, i.e. within the first four cycles of treatment in most responders, thus enabling timely use of transplantation. For patients ineligible for transplant or for those in whom a transplant procedure failed, brentuximab vedotin may represent a feasible effective therapeutic option in everyday clinical practice.