This study evaluated the relationship between crossed cerebellar diaschisis (CCD) and (1) lesion volume and location in the acute phase and 1 week after stroke onset and (2) clinical outcome. Twenty-two patients with cerebral ischemic stroke underwent single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) within 48 h and on day 8 from onset. Interhemispheric asymmetric indices (AI) on SPECT were calculated for medial, intermediate, and lateral zones of the cerebellum. Lesion volumes and locations were obtained from diffusion-weighted MRI. Neurological status and 3-month clinical outcome were evaluated. Within 48 h, lesion locations in the temporal association cortex and pyramidal tract of the corona radiata were independent determinants for the AI of the medial zone (R(2)=0.439). Lesion locations in the primary, premotor, and supplementary motor cortices, primary somatosensory cortex, and anterior part of the posterior limb of the internal capsule were determinants for the AI of the intermediate zone (R(2)=0.785). Lesions in the primary motor cortex, premotor, and supplementary motor cortices and in the genu of the internal capsule were determinants for the AI of the lateral zone (R(2)=0.746). On day 8, the associations were decreased. The AIs of the intermediate and lateral zones and lesion location in the parietal association cortex were independently associated with the 3-month clinical outcome (R(2)>0.555). Acute CCD is a result of functional deafference, while in the subacute phase, transneuronal degeneration might contribute to CCD. CCD in the intermediate and later zones is a better indicator than that in the medial zone.