AbstractWe report a case of primary malignant melanoma of the male urethra in a patient whose penile shaft was successfully preserved, but who proceeded to acute renal failure (ARF) after interferon (IFN)‐β adjuvant immunotherapy. Primary malignant melanoma of the male urethra is rare and usually shows highly malignant potential. Therefore, urologists must often perform phallectomy, which impacts on the patient both sexually and mentally. A 64‐year‐old man presented at Saiseikai Sendai Hospital with asymptomatic gross hematuria and was diagnosed as distal urethral tumor. We predicted the highly malignant potential of this tumor from the urethroscopic finding and from urinary cytological examination. We did not select trans‐urethral resection (TUR), but selected partial urethrectomy.This patient proceeded to ARF 1 month after natural IFN‐β treatment as an adjuvant immunotherapy. As IFN‐β rarely induces the delayed renal failure, urologists should be aware of renal dysfunction after IFN‐β therapy for the treatment of malignant melanoma.