Nervous system Lyme disease and Guillain-Barré syndrome are common neurological conditions that may present with unusual symptoms rendering differential diagnosis difficult. We report the case of a 62-year-old woman presenting with asymmetrical tetraparesis and hyporeflexia. Initially the presumed diagnosis of Guillain-Barré syndrome with a possible functional component was suspected and treatment with intravenous immunoglobulin was initiated. Due to partial response to therapy and further test results including positive serologies and cerebrospinal fluid antibodies for Borrelia, the diagnosis of neuroborreliosis was considered. Further exploring revealed the possibility of exposure to ticks although there was no report of typical skin lesions. Daily physical therapy and appropriate antibiotic treatment with parenteral ceftriaxone resulted in significant improvement of motor symptoms and functional status. The patient was discharged with marked functional improvement and indication for further physical rehabilitation.