This study aimed to explore the heterogeneity of mild cognitive impairment (MCI) and detect differences in regional cerebral blood flow (rCBF) and cognitive function between progressive mild cognitive impairment (PMCI) and stable mild cognitive impairment (SMCI) in order to identify specific changes useful for early diagnosis of dementia. SPECT was performed in 82 MCI subjects and 20 controls using Tc-99m hexamethylpropyleneamine oxime. Cognitive functions were tested in five domains which included episodic memory, semantic memory, visuospatial function, attention, and general cognitive function. After the initial examination, MCI subjects were clinically followed for an average of 2 years. Twenty-eight subjects progressed to dementia and were defined as PMCI at baseline and 54 subjects remained stable and were defined as SMCI at baseline. The baseline rCBF and cognitive function of PMCI, SMCI, and controls were compared. PMCI had decreased relative rCBF in the parietal lobes and increased relative rCBF in prefrontal cortex compared to SMCI and controls at baseline. The cognitive function of PMCI was more severely impaired compared to SMCI with respect to episodic memory and visuospatial and general cognitive function. Both SPECT and neuropsychological tests had moderate discriminant function between PMCI and SMCI at baseline with the area under the receiver operating characteristic (ROC) curve at 75-77%. The combination of these two methods improved the diagnostic accuracy with the area under the ROC curve at 82-84%. Semantic memory and attention were negatively correlated with left prefrontal relative rCBF among the study population. The results show that the clinical heterogeneity of MCI is reflected in different patterns of psychological and CBF changes. Combined SPECT investigation and neuropsychological testing might predict the future development of dementia in patients with MCI.