The purposes of this study were: (1) to determine the prevalence of abnormal 99mTc-HMPAO SPECT scans in patients suffering from persistent post-concussive syndrome (PPCS) after mild closed head injury (CHI); (2) to compare SPECT with structural neuroimaging (MRI and CT) in patients with mild CHI; and (3) to investigate correlations between SPECT and clinical data obtained from the patient sample (neuropsychological testing, demographics, psychiatric diagnoses). Forty-three patients were included. SPECT was read as abnormal in 53% of patients and showed a total of 37 lesions while MRI was read as abnormal in 9% and CT scan in only 4.6% of patients after mild CHI. SPECT appears to be more sensitive in detecting cerebral abnormalities after mild CHI, especially in patients with PPCS symptoms, than either CT or MRI. No statistically significant relationship was found between SPECT scan abnormalities and age, past psychiatric history, history of substance abuse, or history of multiple CHI. Education level did not differ between patients with normal and abnormal SPECT. Current neuropsychiatric symptoms did not seem to have any impact on the results of SPECT scan.