Enhancement of radiation injury to the skin and mucous membranes has been observed with a number of chemotherapeutic agents. A 32-year-old woman with metastatic breast cancer received local radiation therapy to the lumbosacral area. Six weeks later, systemic edatrexate therapy was initiated and a localized painful erythema with edema and a vesicular eruption occurred over the previous site of radiation therapy. Physicians should be aware that edatrexate can cause radiation recall, and that careful use of anti-inflammatory agents may allow continued chemotherapy treatment.