Neuroleptic malignant syndrome (NMS), characterized by catatonic behavior, generalized muscular rigidity, hyperthermia and autonomic dysfunction, can suddenly arise in patients treated with neuroleptic agents and carries a high mortality rate even today. A case of NMS due to i.m. therapy with haloperidol decanoate is reported in this paper, characterized by sustained course and a severe relapse due to a different therapy with another neuroleptic agent. The patient however, after a prolonged remission from the relapse, was able to resume long term therapy with neuroleptic drugs. The importance of monitoring blood levels of CPK during the follow-up and the effectiveness of therapy with bromocriptine and dantrolene in confirmed. Although the patient presented a good clinical response, she developed permanent cerebral and muscular damage. A wide review of the literature on NMS is reported to throw light on this syndrome, whose recognition and prompt diagnosis are necessary to reduce mortality.