Leptomeningeal spread of childhood primary central nervous system (CNS) neoplasms, also known as leptomeningeal disease (LMD), significantly affects prognosis and treatment. Lumbar cerebrospinal fluid (CSF) cytology and spinal magnetic resonance imaging (MRI) are considered critical for diagnosis of LMD. It has been suggested that either CSF cytology or spinal MRI alone would miss LMD in up to 18% of children with CNS neoplasms. To determine the rate of LMD and the concordance of these two tests at our institution, we analyzed the results of concurrent CSF cytology and spinal MRI (tandem CSF/MRI) performed at the UCSF Pediatric Neuro-oncology Division. We identified all patients who underwent tandem CSF and MRI analysis during their treatment between 1990 and 2005. There were 127 tandem analyses from 78 patients, of which 115 were concordant. Among the remaining 12 discordant tandem analyses, spinal MRI was positive and CSF was negative for tumor in 8 patients, while CSF was positive and spinal MRI was normal in four others. In all discordant cases, positive spinal MRI was often associated with aggressive disease. Positive CSF cytology correlated with aggressive disease only in one patient who had evidence of disseminated intracranial tumor on MRI. In the absence of intracranial tumor spread or LMD on MRI, a positive CSF cytology did not correlate with aggressive disease or recurrence. Even though the number of cases is limited, our findings suggest that a positive CSF cytology with no other corroborating evidence of tumor spread or recurrence should be interpreted with caution.