Hypertrophic olivary degeneration (HOD) is associated with lesions within the dento-rubro-olivary pathway or Guillain-Mollaret triangle and may be associated clinically with palatal tremor. Here we report HOD on brain magnetic resonance (MR) imaging in three patients with progressive mitochondrial syndromes in the absence of palatal tremor. Two of the patients were found to have identical compound heterozygous mutations in the POLG gene, encoding the catalytic subunit of the mitochondrial DNA polymerase-γ, but presented with different clinical phenotypes. The first patient displayed the clinical syndrome of sensory ataxia, neuropathy, dysarthria, and ophthalmoparesis (SANDO), while the second patient was affected by a neurological disorder consisting of an ophthalmoplegia, myopathy, and neuropathy. The third case was a child with Leigh syndrome due to SURF1 gene mutations, who presented with a generalized tremor. We discuss the brain MR imaging findings in these three cases along with a literature review on the MR features of previously reported cases of patients with POLG gene mutations and Leigh disease due to SURF1 gene mutations. Our findings suggest that the presence of HOD, in the appropriate clinical setting, should alert the clinician to the possibility of a mitochondrial disorder and the need to screen for mutations in POLG and SURF1 genes.