Pazopanib is an oral multi-kinase inhibitor approved for the treatment of advanced renal cell carcinoma (RCC). It is an anti-angiogenic agent, which blocks the activation signaling pathways of tyrosine kinases and prevents the activities of primarily vascular endothelial growth factor receptors (VEGFR)-2 and VEGFR-3, which are important in lymphangiogenesis. Herein, we report a patient with advanced RCC who developed asymptomatic left-sided chylothorax under pazopanib therapy. Chylothorax developed in the 16th month and gradually increased until it was diagnosed by thoracentesis in the 22nd month. The development of chylothorax was attributed to pazopanib therapy after ruling out all possible traumatic and nontraumatic etiologies. The 'Adverse Drug Reaction Probability Scale' revealed a total score of 6, which fell into 'probable' category. Chylothorax regressed significantly 5 weeks after the discontinuation of pazopanib therapy.