Spindle cell pseudotumors may occur due to mycobacterial infection, especially in immunocompromised hosts including those with AIDS. They have been reported from many body sites; the lymph nodes are predominantly involved, most frequently associated with Mycobacterium avium complex infection. To the best of our knowledge, Mycobacterium-associated spindle cell pseudotumors have not been previously described in the brain stem and in association with mixed mycobacterial infection.We describe a man with AIDS who presented with right hemiparesis and truncal ataxia. Magnetic resonance imaging revealed enhancing nodular lesions at the cerebral peduncle and medulla. A mycobacterial spindle cell pseudotumor was diagnosed on surgical specimens. Blood and brain tissue cultures grew Mycobacterium haemophilum and Mycobacterium simiae.To our knowledge, this is the first case of spindle cell pseudotumor of the brain associated with M. haemophilum and M. simiae mixed infection.