Establishing a differential diagnosis in psychiatry may be very laboring. The authors aim to illustrate diagnostic complexity and its therapeutic implications, through the presentation and discussion of a presumable dementia clinical picture. We present the case of a fifty six-year old woman, attending our outpatient clinics since her twenties with the diagnosis of schizoaffective disorder. On April of 2007 the patient was admitted to a fifteen-day hospitalization due to psychotic symptoms, which remitted with therapeutic doses of risperidone and ansiolytics. One week after being discharged the patient was readmitted to the hospital due to an abrupt onset of a clinical picture characterized by behavioral changes, motor agitation and repetitive behaviors, refusal to eat, depressive mood, mystical delusions, hallucinatory activity, loss of insight, and severe impairment in occupational and social functioning. Although several clinical trials of antipsychotics, antidepressants and mood stabilizers were tried, along with electroconvulsive therapy, her general clinical state has remained unchanged for the fifteen months of hospitalization. Blood and urine examinations, tumoral markers, infectious and immunological study, lumbar puncture, neuroimaging, EEG and brain biopsy were performed, without conclusive results. We consider that the presumptive diagnosis is a Frontotemporal Dementia (FTD). Due to this entity’s distinct neuropsychiatric manifestations, its diagnosis can be challenging. This presentation also emphasizes the importance of a holistic analyzes of clinical situations and of a multidisciplinary approach.