Pemetrexed is a novel antimetabolite that targets multiple enzymes in the folate pathway, and has exhibited clear antitumor activities in the treatment of malignant pleural mesothelioma and non-small cell lung cancer. Although many adverse events of pemetrexed, such as bone marrow suppression, have been reported, edema of the eyelid has been previously reported in only one case (0.2%, n=519), according to the Pemetrexed Clinical Investigator's Brochure, April 2005 version. We experienced a patient who developed the valuable edema of the eyelid. We believe that medical oncologists should be aware of this rare adverse event, although the mechanism responsible for it is not yet known.