A 60-year-old man with metastatic transitional cell carcinoma of the bladder was treated with weekly methotrexate injections, each followed by leucovorin rescue. After two to three hours of sun exposure, he experienced a mild sunburn erythema on his lower extremities in areas not chronically sun exposed. He received methotrexate the next day. More than one week later, following another dose of methotrexate, he experienced a second-degree burn in the areas of the prior sunburn, with sparing of chronically exposed areas on his face, neck, and arms. We discuss here the reactivation and exacerbation of sunburn by methotrexate and other chemotherapeutic agents, the unique features of delayed onset and selective skin involvement in our case, and the need for sun protection in patients receiving these drugs.