Classic hairy cell leukemia (HCL) is a rare indolent B‑cell-lymphoproliferative disorder, first described as a distinct disease entity in 1958. After more than two decades without effective chemotherapeutic options and a dismal prognosis of less than 5 years, only the introduction of interferon‑α (IFN‑α) allowed for response rates between 80–90 % and survival improvement. Nowadays, however, patients are rarely treated with IFN-α as purine analogues were found to be highly effective in HCL facilitating a near normal life span in most cases. Moreover, novel therapeutic tools for patients with relapsed or refractory disease after purine analogues have emerged such as rituximab and, more recently, vemurafenib. In the absence of long-term safety data for these novel agents, however, IFN-α may still represent a viable therapeutic option when the profound immunosuppressive side effects of purine analogues are to be avoided. We herein report a HCL patient, who has received multiple lines of therapy, including pentostatin, cladribine, and a total of 164 months of treatment with IFN‑α yielding long-term disease control. Our case illustrates that long-term administration of IFN-α with adequate dose-adjustments according to toxicity and disease activity is feasible in HCL and may still be a viable therapeutic option when purine analogues are considered unsuitable.