We report two patients who developed isolated visual symptoms and signs as initial manifestations of Creutzfeldt-Jakob disease (CJD). Both patients had normal conventional T1- and T2-weighted brain magnetic resonance (MR) images; in one patient, early cortical abnormalities were detected by diffusion-weighted and fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). Results from the cerebrospinal fluid assay for the 14-3-3 brain protein were also negative in one patient, despite pathologic confirmation of CJD at autopsy. The Heidenhain variant of CJD should be considered in all patients who present with isolated visual manifestations, including homonymous hemianopsia and normal conventional brain MRI. Diffusion-weighted and FLAIR MRI may demonstrate early cortical abnormalities in patients with CJD. The CSF assay for the 14-3-3 protein may be normal, even in pathologically confirmed cases.