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This report highlights the continuing public health challenge of Lyme disease in states with high incidence and demonstrates its emergence in neighboring states that previously experienced few cases. Educational efforts should be directed accordingly to facilitate prevention, early diagnosis, and appropriate treatment. As Lyme disease emerges in neighboring states, clinical suspicion of Lyme disease in a patient should be based on local experience rather than incidence cutoffs used for surveillance purposes. A diagnosis of Lyme disease should be considered in patients with compatible clinical signs and a history of potential exposure to infected ticks, not only in states with high incidence but also in areas where Lyme disease is known to be emerging. These findings underscore the ongoing need to implement personal prevention practices routinely (e.g., application of insect repellent and inspection for and removal of ticks) and to develop other effective interventions.