Introduction. Pyoderma gangrenosum (PG) is a rare, ulcerating neutrophilic dermatosis often associated with inflammatory bowel disease, rheumatoid arthritis, and myeloproliferative disorders. The classic description of PG includes irregularly shaped ulcers with undermined edges with a gun-metal gray or violaceous hue. The etiology remains unclear but appears to be related to genetically predisposed dysregulation of the innate immune system. Diagnosis of PG can be difficult as it can present with symptoms similar to cutaneous infections including erythema, edema, ulceration, fever and leukocytosis. Surgical procedures are generally contraindicated in patients with PG due to the risk of pathergy, excessive cutaneous injury, or ulceration in response to trauma. Case Report. The authors report the development of PG with the initiation of chemotherapy in a 46-year-old woman with breast cancer. The patient had a complicated clinical course after multiple surgical debridements due to an initial misdiagnosis of necrotizing fasciitis. The patient’s rapid onset of post-procedural ulceration was consistent with the pathergy of PG. The diagnosis of PG was confirmed by skin biopsy, which revealed a diffuse neutrophilic infiltrate, and with the patient’s negative cultures and response to steroids. The patient was treated with perioperative prednisone and intravenous immunoglobulin prior to a mastectomy for her breast cancer. The surgery was not complicated by pathergy. Conclusions. This unique case highlights the challenging aspects in the medical and perioperative management of active PG in a patient with breast cancer.