Paraffinoma is a destructive complication of paraffin oil injection, usually associated with massive tissue destruction, thus requiring radical surgery and subsequent complex reconstruction. Although breast and penile paraffinomas have been widely described and their management is quite standardized, paraffinomas of the knee are still rare and only few case reports or small case series are available in the current literature. We describe the case of a 77-year-old man with a large paraffinoma of the right knee that occurred after self-injection of paraffin oil, 58 years before. He underwent wide surgical resection of the soft tissues overlying the knee and subsequent two-stage reconstruction by using acellular dermal matrix and, after 20 days, split-thickness skin grafts. Follow-up after 16 months showed no signs of skin ulcerations or inflammation, with an overall improvement in function. Even though conventional flap reconstructions may be still useful, the authors believe that acellular dermal matrices represent a safe, reliable, and less invasive alternative for challenging soft tissue reconstructions even in elderly patients with multiple medical problems.