A female patient with a critical soft tissue defect after elective knee replacement surgery was transferred to our department for reconstruction. As wounds were rapidly progressing, necrotizing fasciitis was initially suspected but eventually ruled out by histopathological analysis. A 50 × 15 cm defect was then reconstructed by means of a combined Parascapular and latissimus dorsi flap before, a couple days later, the patient developed tender pustules and ulcers involving the flap as well as the donor site. Attempts of excising necrotic areas not only continued to fail but seemed to worsen the patient's wound and overall condition. Eventually, pyoderma gangrenosum (PG) was diagnosed and local and systemic therapy was initiated but treatment proved to be challenging and insufficient at first. Being an extremely aggressive disease, early diagnosis is crucial and PG should always be suspected when rapidly progressive ulceration on surgical sites is observed.