Background: Dermatologists, or pathologists, occasionally need to decide whether or not to continue methotrexate therapy in a patient with an identifiable risk factor for liver fibrosis, in this instance heterozygous α₁-antitrypsin deficiency. Case Presentation: We relate our experience with an elderly male patient, diagnosed as having α₁-antitrypsin deficiency on a liver biopsy, genotypically confirmed as PiMZ. He had been receiving methotrexate for psoriasis for 17 years with a cumulative dose of 7,200 mg. He was monitored by biochemical profiling and interval (10) liver biopsies. Non-specific changes were seen on liver histology although grade 1 liver fibrosis was seen in his last 2 biopsies. Conclusion: We suggest that methotrexate therapy is relatively safe in patients with heterozygous α₁-antitrypsin deficiency, with no other risk factor. We however advise that the risk of fibrosis should be monitored and that the patient receives appropriate counselling.