The differential diagnosis of multiple sclerosis is extensive and it can be challenging to diagnose initially in the absence of pathognomonic clinical features. Furthermore, these patients can also develop other diseases during their course of treatment, which usually lasts for many years. Some conditions, such as primary central nervous system lymphoma, can mimic clinically some of the symptoms prominent in multiple sclerosis. Early treatment with corticosteroids can also dramatically improve patient symptoms in both conditions. We report a case of a man diagnosed with histologically confirmed relapsing remitting multiple sclerosis who subsequently developed histologically confirmed primary central nervous system lymphoma. The course of his disease and treatment are presented and the current literature reviewed.