Penile calciphylaxis is a rare and highly morbid condition mainly affecting diabetic patients with chronic renal failure (CRF). It is characterized by ischemic skin ulceration and necrosis secondary to dystrophic calcification of the subcutaneous penile tissue and penile arterioles. We report a 52-year-old male with a 6-year history of diabetes mellitus and CRF on hemodialysis, who presented with a painful penile necrotic lesion in the last three weeks. He firstly treated with medical treatment, which was failed. Then underwent total penectomy. The histopathology result confirmed the diagnosis of penile calciphylaxis. Unfortunately, he passed away due to septic shock and multisystem organ failure ten days after surgery. In conclusion, the diagnosis of penile calciphylaxis must be evoked in the presence of any minimal necrotic penile lesion in a patient with CRF; this will initiate quick medical and/or minimally invasive surgical treatment to improve the patient's prognosis and avoid serious complications.