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Background: Mills' syndrome is an extremely rare degenerative motor neuron disorder first described by Mills in 1900, but its nosological status is still not clear. We aimed to analyze the clinical features of Mills' syndrome., Case Summary: Herein, we present 3 cases with similar features as those described in Mills' original paper and review the related literature. Our patients showed middle- and older-age onset, with only upper motor neuron symptoms evident throughout the course of the disease. Spastic hemiplegia began in the lower extremity with a unique progressive pattern., Conclusion: We consider that Mills' syndrome is a unique entity of motor neuron disorder with an N-shaped progression. Clinicians should maintain a high index of suspicion for the diagnosis of Mills' syndrome when the onset involves lower extremity paralysis without evidence of lower motor neuron or sensory involvement., Competing Interests: Conflict-of-interest statement: The authors did not provide a conflict of interest statement., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)