Several chemotherapeutic agents are known to induce lacrimal drainage stenosis and obstruction, resulting in epiphora. Pemetrexed is one such drug and is used in the management of mesotheliomas and non-small cell lung carcinomas. Pemetrexed inhibits folate metabolism at multiple levels. The present case is the second report of pemetrexed induced punctal and canalicular stenosis, but the first to document dacryoendoscopy findings and report balloon puncto-canaliculoplasty as a minimally-invasive treatment option.