Fowlpox is a contagious viral disease of poultry, ranked as the third most important cause of mortality in Nigerian indigenous chickens. The present study confirms an outbreak of fowlpox in a flock of 500 Isa brown, 11-weeks-old pullets in Zaria, Kaduna State, Nigeria. The pullets were managed under deep litter system and previously vaccinated with live attenuated vaccine (ABIC biological laboratories Ltd. Israel) at 8-weeks old. They had gross lesions suggestive of cutaneous fowlpox on skin of the head region with 58% morbidity but persistent low mortality rate of 13.8%. Fowlpox virus was isolated from the cutaneous lesions using chorioallantoic membrane (CAM) inoculation in 9 to 11-day-old embryonated chicken eggs based on the presence of opaque-white pock lesions, then confirmed by Agar Gel Immuno Diffusion test using homologous known fowlpox virus (antigen) and antisera. Specific antibodies to fowlpox virus were quantified from the sera of the chickens using an indirect ELISA (Abbkine, Inc, China). The case was managed using; Intramuscular injection of oxytetracycline (TLA), topical applications of oxytetracycline spray as well as oral administrations of Doxygen® and vitamins. Apparently healthy chickens were revaccinated against fowlpox and the pen was thoroughly cleaned, washed, and disinfected. This report had shown an occurrence of vaccine failure, alongside a promising management option and highlighted the significance of vaccination with strict biosecurity measures in the control of fowlpox in Nigeria.