Cutaneous squamous cell carcinoma (cSCC) currently affects over 700 000 patients per year in the USA alone, and its incidence continues to rise in recent years. A known risk factor for cSCC is chronic inflammation; a cSCC that develops at a site of chronic inflammation is known as Marjolin's ulcer. We present the case of a 76-year-old man with end-stage renal disease requiring chronic haemodialysis who developed an invasive cSCC at the cannulation site of an underlying arteriovenous (AV) fistula. In this instance, treatment with standard surgical excision or Mohs surgery would pose unique risks associated with injury to an otherwise functional AV fistula. Thus, the lesion was treated with electron beam radiation therapy, which offers a similar efficacy to surgery while minimising risk to the fistula. This resulted in a successful oncological outcome with no complications.