Abstract Importance: To describe a case of predominantly motor polyradiculopathy secondary to Lyme disease that can mimic motor neuron diseaseand has been rarely reported. Observations: A 64 year-old man presented with a one-month history of rapidly progressive weakness involving bulbar, upper limb and lower limb muscles. The physical examination showed widespread weakness, atrophy, fasciculation and brisk reflexes. The initial electrodiagnostic test showed widespread active and chronic denervation findings. The initial physical and electrodiagnostic findings were suggestive of Amyotrophic Lateral Sclerosis (ALS). However blood serology indicated possible Lyme disease. Thus, the patient was treated with doxycycline. The clinical and electrodiagnostic findings were resolved with the treatment. Conclusion and Relevance: The diagnosis of Lyme disease can be very challenging and it can mimic other neurological disorders such as ALS or Guillain-Barre syndrome (GBS). Careful and detailed examination and investigation are required to confirm the diagnosis and to prevent misleading inaccurate diagnoses.