There is no diagnostic biological marker in multiple sclerosis. Thus, its diagnosis is based on clinical criteria. These criteria can also be found in other conditions. Lyme disease is currently among them. In a late period of the disease demyelinating involvement of central nervous system can develop, and multiple sclerosis can be erroneously diagnosed. We have evaluated a series of 55 patients with a definite diagnosis of multiple sclerosis, and we have found evidence of infection by the causative organism of Lyme disease in three. We describe the three patients and we discuss the relationship between both conditions. We conclude that it is important to consider Lyme disease as a diagnostic possibility in patients with neurological disease of unknown etiology such as multiple sclerosis.