Acral erythema is a rare cutaneous reaction that has been associated with various chemotherapy regimens. Most occurrences have been described in adult patients. Recently, methotrexate has been implicated in the development of acral erythema; however, pediatric reports are few. All of the reports in the pediatric and adult literature have described patients receiving moderate to high-dose intravenous methotrexate. Here, we describe an instance of standard-dose oral methotrexate-associated acral erythema in a young girl with acute lymphoblastic leukemia, and review the recent literature as it relates to pediatric patients.