Calciphylaxis is a rare, life-threatening syndrome of vascular calcification and microvascular occlusion in the dermis and panniculus, leading to painful ischemic lesions. While historically tied to end-stage kidney disease, non-uremic calciphylaxis (NUC) has been increasingly recognized in patients with normal kidney function but with other risk factors, including systemic autoimmune diseases, hypercoagulable states or chronic steroid therapy. Diagnosing NUC in patients with such underlying autoimmune diseases is challenging. Its initial clinical presentation of indurated subcutaneous nodules and plaques closely mimic other conditions such as lupus profundus, a rare variant of lupus erythematosus characterized by lobular panniculitis. As the management for both conditions differ, misdiagnosis or delayed diagnosis can lead to inappropriate immunosuppression, delayed targeted therapy and worsening tissue ischemia. We present the case of a 34-year-old woman with previously known systemic lupus erythematosus (SLE) and prior biopsy-proven lupus profundus, who developed a chronic, non-healing thigh ulcer over the original lesion, subsequently diagnosed as NUC upon repeat biopsy.