Paclitaxel is highly active against a variety of solid tumors including breast lung, ovarian and head and neck cancer. Although peripheral neurotoxicity is well-known side effect, central nervous system (CNS) toxicity-related standard dose of paclitaxel is extremely uncommon, because paclitaxel dose not cross the blood-brain barrier and is not detectable in the cerebrospinal fluid. We present a patient with advanced stage breast carcinoma who developed acute and spontaneous resolving encephalopathy after weekly dose of paclitaxel. The patient did not have brain metastasis, or prior whole-brain irradiation, or any type of neurosurgery. Radiological imaging studies showed no abnormalities. CNS toxicity of paclitaxel should be kept in mind in patients without a previous history of brain metastasis or brain irradiation and even with low weekly doses.