Central nervous system (CNS) manifestations are seen in two-thirds cases of familial haemophagocytic lymphohistiocytosis (HLH). Isolated CNS-HLH is described as a rare entity characterised by isolated neuroinflammation without fulfilling diagnostic criteria for evidence of systemic inflammation in mutation-proven familial HLH due to additional genetic modifiers. We describe one such female preschooler who presented to us with the fever of unknown origin spanning over a year and was a diagnostic dilemma. Only two out of the available seven criteria were fulfilled for systemic HLH in the index child. A neuroimaging study done as part of the investigation for seizure led to suspicion of CNS-HLH, and the final diagnosis was established by whole-exome sequencing, which revealed PRF1 mutation. Knowledge about isolated CNS-HLH will help keep it a differential diagnosis in cases where cerebrospinal fluid and neuroimaging findings may suggest a neuroinflammatory disorder. It may lead to early diagnosis and prompt therapy, thereby preventing long-term neurological sequelae.