A new clinical study suggests that narrow Band Ultraviolet B (NB-UVB) phototherapy is effective, well-tolerated treatment for antihistamine-refractory chronic spontaneous urticaria, offering a viable alternative to oral cyclosporine. CSU, marked by persistent hives and itching lasting more than 6 weeks, often leaves patients and clinicians struggling to find effective treatment beyond antihistamines. Cyclosporine, though effective, is typically reserved as a third-line option due to concerns about toxicity and rebound flares. The current study highlights NB-UVB phototherapy as a promising contender in this treatment landscape. This trial enrolled 50 patients whose CSU had failed to respond to maximum-dose antihistamines. The participants were divided into 2 groups: one received NB-UVB phototherapy 3-times weekly, while the other was prescribed cyclosporine at 3 mg/kg/day. Both regimens lasted 90 days, with outcomes tracked for another 90 days post-treatment. This study assessed patients primarily using the Urticaria Activity Score over 7 days (UAS7). Secondary measures included the Urticaria Control Test (UCT), the Chronic Urticaria Quality of Life (CU-QoL) questionnaire, and changes in serum biomarkers such as IL-6, IL-31, and IgE. Both treatment groups showed significant symptom relief by Day 15. Cyclosporine worked faster, providing rapid reductions in UAS7, but patients frequently experienced rebound flares after discontinuation. NB-UVB, on the other hand, produced more gradual but longer-lasting control, with sustained improvements noted even after therapy ended. When comparing efficacy, NB-UVB met the non-inferiority criteria, meaning it was not significantly less effective than cyclosporine in reducing UAS7 scores. Quality of life measures (CU-QoL) improved in both groups, while UCT scores confirmed patients reported better control of their condition under either regimen. In terms of biomarkers, both groups experienced reductions in serum IgE. However, the cyclosporine group showed a more pronounced decrease in inflammatory markers IL-6 and IL-31, aligning with the drug’s systemic immunosuppressive effect. NB-UVB proved to be well tolerated with minimal side effects, reinforcing its suitability for long-term disease management. Cyclosporine, although effective, carried its usual risks, and the flare-ups post-discontinuation raised concerns about dependency. The limitations of this study include its single-center design and relatively short follow-up of 90 days after treatment cessation. Broader, multi-center research with extended monitoring will be essential to validate these findings. Overall, the results place NB-UVB phototherapy firmly on the map as a potential alternative to cyclosporine in antihistamine-refractory CSU. Roshini, N., Mehta, H., Bishnoi, A., Kumar, V., Kumar, A., Parsad, D., & Kumaran, M. S. (2025). Narrow band ultraviolet B phototherapy versus oral cyclosporine in the treatment of chronic urticaria. Photodermatology, Photoimmunology & Photomedicine, 41(5),.https://doi.org/10.1111/phpp.70050