This report mainly presents the clinical and laboratory findings in a group of 15 primary hemophagocytic lymphohistiocytosis patients with central nervous system involvement (group 1) and compares some of the findings with those of 13 hemophagocytic lymphohistiocytosis patients without central nervous system involvement (group 2). Statistical analysis showed that age and sodium level at diagnosis were significantly higher while alanine aminotransferase and bilirubin levels were significantly lower in group 1 than group 2 (P < .05). There were no statistically significant differences between the 2 groups in the other clinical, laboratory, and overall survival parameters. Three patients in group 1 initially had central nervous system involvement in the absence of systemic findings, which led to the initial misdiagnosis of these patients as central nervous system disorders other than hemophagocytic lymphohistiocytosis. © 2008 Sage Publications.