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Calciphylaxis, a rare obliterative small vessel vasculopathy associated with diabetes mellitus (DM), end-stage renal disease (ESRD), portends a poor prognosis. Because penile involvement is rare, agreement on appropriate diagnosis and management is unclear.To determine the role and effect of penile biopsy for diagnosis and management of penile calciphylaxis.Medical records of three penile calciphylaxis patients from our institution were evaluated. Data collected included age, history of DM, ESRD, and hemodialysis (HD) status, serum calcium (Ca), Ca × phosphorous product (C × P), parathyroid hormone (PTH), performance of biopsy, presence of non-penile cutaneous lesions, intervention, survival, and time from diagnosis to death. PubMed Search for relevant publications from 1995 to 2012 was performed to identify case reports of penile calciphylaxis that provided the same clinical data obtained from the 3 patients from our institution.Clinical evidence for outcomes in patients with penile calciphylaxis after biopsy of penile lesion compared to those without biopsy.A total of sixteen patients were identified in the literature and in our institution with clinical data of interest. Overall, 10/16 (62.5%) patients identified with penile calciphylaxis had a penile biopsy, and 7/10 (70%) experienced disease progression, while only 3/10 (30%) stabilized. Mean time to death in this patient population was short, approximately 6.5 months, regardless of type of intervention.Based on the results of our study, we argue that conservative measures should be employed as first line therapy for penile calciphylaxis. More importantly, secondary to likely resultant progression of necrosis, penile biopsy is not only unnecessary for diagnosis of penile calciphylaxis, but is also harmful and contraindicated. Cimmino CB and Costabile RA. Biopsy is contraindicated in the management of penile calciphylaxis. J Sex Med 2014;11:2611–2617.