The early detection of major depression in elderly individuals who are at risk of developing the disease is of prime importance when it comes to the prevention of geriatric depression. We used resting-state functional magnetic resonance imaging (fMRI) to examine changes in regional homogeneity (ReHo) of spontaneous activity in late-life subthreshold depression (StD), and we evaluated the sensitivity/specificity performance of these changes. Nineteen elderly individuals with StD and 18 elderly controls underwent a resting-state fMRI scan. The ReHo approach was employed to examine whether StD was related to alterations in resting-state neural activity, in the form of abnormal regional synchronization. Receiver operating characteristic curve analysis and the Fisher stepwise discriminant analysis were used to evaluate the sensitivity/specificity characteristics of the ReHo index in discriminating between the StD subjects and normal controls. The results demonstrated that, compared to controls, StD subjects display lower ReHo in the right orbitofrontal cortex (OFC), left dorsolateral prefrontal cortex (DLPFC), left postcentral gyrus (PCG), and left middle frontal and inferior temporal gyri, as well as higher ReHo in the bilateral insula and right DLPFC. The left PCG and the right DLPFC, OFC, and posterior insula, together reported a predictive accuracy of 91.9%. These results suggest that the regional activity coherence was changed in the resting brain of StD subjects, and that these alterations may serve as potential markers for the early detection of StD in late-life depression.