It is unclear what key symptoms differentiate Myalgic Encephalomyelitis (ME) and Chronic Fatigue syndrome (CFS) from Multiple Sclerosis (MS). The current study compared self-report symptom data of patients with ME or CFS with those with MS. The self-report data is from the DePaul Symptom Questionnaire, and participants were recruited to take the questionnaire online. Data were analyzed using a machine learning technique called decision trees. The best discriminating symptoms were from the immune domain (i.e., flu-like symptoms and tender lymph nodes), and the trees correctly categorized MS from ME or CFS 81.2% of the time, with those with ME or CFS having more severe symptoms.