Our objective was to ascertain in a prospective case series how often brain single photon emission computed tomography (SPECT) neuroimaging adds relevant information for diagnosis and/or treatment beyond current standard assessment tools in complex psychiatric cases. Charts of 109 consecutively evaluated outpatients from four psychiatrics clinics that routinely utilize SPECT imaging for complex cases were analyzed in two stages. In stage one, psychiatrists reviewed detailed clinical histories, mental status exams, and the structured clinical interview for DSM-IV, but not the results of SPECT studies, assigned a diagnosis based on DSM-IV criteria, and then developed a comprehensive treatment plan. In stage two, evaluators were given access to the SPECT studies for each patient. The addition of SPECT modified the diagnosis or treatment plan in 78.9% (n=86; rated level 2 or 3 change) of cases. The most clinically significant changes were undetected brain trauma (22.9%), toxicity patterns (22.9%) and the need for a structural imaging study (9.2%). Specific functional abnormalities were seen as follows that potentially could impact treatment: temporal lobe dysfunction (66.1%) and prefrontal hypoperfusion (47.7%). SPECT has the potential to add clinically meaningful information to enhance patient care beyond current assessment tools in complex or treatment resistant cases.