Methotrexate-related hematologic toxicity may include leukopenia, thrombocytopenia, megaloblastic anemia, and pancytopenia. We report a woman with hypertensive renal disease who was receiving hemodialysis and developed pancytopenia following a single intradermal infiltration of 25 mg of methotrexate. Caution should be exercised when considering the use of either systemic or intralesional methotrexate therapy in patients with risk factors that have been implicated in the development of adverse hematologic side effects: renal dysfunction, possible drug interactions, and advanced age.