We report a 37-year-old patient with gastric cancer who suffered two distinct episodes of generalized tonic-clonic seizures during ongoing chemotherapy with cisplatin and 5-fluorouracil. Cranial MRI revealed reversible posterior leukoencephalopathy (RPL) that remitted completely without any specific therapy after discontinuation of the chemotherapeutic drugs. Interestingly, RPL occurred repeatedly in our patient following the single chemotherapy cycles, which has not been described so far. This syndrome is clinically relevant for differential diagnosis of bilateral ischemia of the posterior cerebral arteries. An overview of the literature and necessary diagnostic procedures is given.