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Cutaneous squamous cell carcinoma is the second most common form of skin cancer and accounts for 20% of cutaneous malignancies. We report the case of a patient who presented with a complaint of nonhealing wounds following radiation therapy for the treatment of noninvasive squamous cell carcinoma of both lower extremities. Initial biopsies of the wounds were benign. However, a second biopsy performed approximately 2 months later was found to be positive for invasive squamous cell carcinoma. This case uniquely exemplifies that all nonhealing wounds should be viewed with a critical eye for possible malignancy even in the presence of previous negative biopsy. This is especially true for radiation wounds that may be prone to malignant transformation or recurrence. (J Am Podiatr Med Assoc 101(4): 360–362, 2011)