| Sumario: | Simple Summary: Post-surgical pyoderma gangrenosum is an uncommon autoinflammatory disorder that can closely mimic postoperative infection, thereby complicating timely diagnostic evaluation and management. This report describes a case of rapidly progressive postoperative inflammation following breast cancer surgery with immediate reconstruction, refractory to antimicrobial therapy and consistently negative on microbiological investigation. Histopathological examination revealed a sterile neutrophilic infiltrate, with prompt clinical improvement after immunosuppressive therapy. This case underscores the importance of considering this rare entity when postoperative inflammatory findings are incongruent with an infectious etiology. Post-surgical pyoderma gangrenosum is a rare neutrophilic dermatosis that may occur after surgical procedures, mimicking a wound infection. Early recognition is crucial to prevent unnecessary debridement and worsening of lesions due to pathergy. We report the case of a 67-year-old woman who underwent nipple-sparing mastectomy for invasive breast carcinoma with immediate reconstruction using a tissue expander. In the early postoperative period, she developed an extensive sterile necrotic–ulcerative inflammation of the left breast, unresponsive to broad-spectrum antibiotics and repeated surgical revisions. Histopathology revealed an aseptic neutrophilic infiltrate, confirming the diagnosis of post-surgical pyoderma gangrenosum. The patient responded favorably to high-dose corticosteroid therapy, achieving complete wound healing and definitive reconstruction with a TRAM flap. This case highlights the importance of considering post-surgical pyoderma gangrenosum in the differential diagnosis of inflammatory postoperative complications in breast oncology surgery. Prompt diagnosis and early initiation of immunosuppressive therapy within a multidisciplinary approach are key to preserving tissues and ensuring optimal functional and aesthetic outcomes.
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