Introduction: Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is a rare but dreaded condition in patients with chronic renal failure (CRF), whether they are on dialysis or not. Case report: A 67-year-old woman with a 10-year history of chronic renal failure, undergoing hemodialysis, presented with bilateral mastitis characterized by severe lancinating pain and non-healing tissue loss despite medical treatment with antibiotics and anti-inflammatory drugs. Mammography provided limited imaging findings. The diagnosis of calciphylaxis was established after bilateral surgical biopsy. Discussion: Calcific uremic arteriolopathy, or calciphylaxis, is a rare but life-threatening disease associated with chronic renal failure. Its diagnosis can be challenging. Skin biopsy is considered the gold standard for establishing the diagnosis, but it is not without risks. Recognizing typical skin lesions is important for initiating appropriate management. The management of these patients is multidisciplinary and involves several aspects. In certain cases, the clinical situation may not allow for a cure, and palliative care options will be proposed. Conclusion: Calcific uremic arteriolopathy is a dreaded condition that primarily occurs in patients with known chronic renal failure, whether they are on dialysis or not. The prognosis is very grim. It relies on a careful examination of the lesions and the exclusion of various differential diagnoses. A multidisciplinary approach is essential to prevent the progression of the lesions and facilitate healing.