Central nervous system (CNS) involvement in acute lymphoblastic leukaemia is associated with a poor prognosis, making accurate detection essential for risk stratification and guiding treatment decisions. Cytomorphology of cerebrospinal fluid has been the gold standard for assessing CNS involvement. However, it has limited sensitivity, particularly in low cell counts. Flow cytometry has emerged to be a valuable diagnostic tool with higher sensitivity, particularly in paucicellular samples. Occult CNS disease has emerged as a newer group where the cytomorphology shows no blasts while the flowcytometry records the leukemic blast population. Flow cytometry remains challenging due to the lack of standardised positivity criteria, unclear prognostic implications and management strategies for occult CNS diseases. This systematic review critically examines the methodologies for detecting leukemic infiltration within cerebrospinal fluid, focusing on conventional cytomorphology and multiparameter flow cytometry. In addition, it also addresses key pre-analytical variables, such as cerebrospinal fluid volume, processing time, and total nucleated cell counts. These parameters significantly influence the accuracy of both methods. Future research is required to establish uniform diagnostic guidelines and assess the clinical relevance of occult CNS disease in acute lymphoblastic leukaemia.