Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of pathologic immune activation. Central nervous system (CNS) affection, referred to as “CNS-HLH”, is an especially challenging diagnosis when it occurs as the initial or only presentation of the disease. Our aim is to highlight the HLH as a possible diagnosis in children with different neurological manifestations. Methods: A descriptive study of 4 patients from our institution who have presented with neurological manifestations either as the initial or only presentation of HLH. Case description: The patients’ age ranged from 2.5 to 12 years at first presentation. All patients were previously developmentally and neurologically normal and presented with psychomotor regression ±convulsions. They were misdiagnosed and treated as recurrent meningitis, acute disseminated encephalomyelitis, and metachromatic leukodystrophy. They did not respond to treatment and have been referred for reassessment. Two of them had grey hair suspicious of Griscelli syndrome type II; one had a worrisome family history which prompted the search for HLH. All of them had fulfilled HLH-2004 diagnostic criteria (three later confirmed by genetic testing) and have started treatment with improvement of their neurological condition. Of note, three of them have later developed other systemic manifestations of HLH but one child didn't develop any systemic manifestation during her 2 years follow up period. Conclusion: Raising awareness about CNS-HLH is essential to prevent delayed diagnosis and improve prognosis. Systemic manifestations of HLH can be delayed beyond the neurological one so keeping a high index of suspicion is mandatory, particularly in resources limited countries.