Most modern haematology analysers have a dedicated body fluid mode for cell counts of body fluids. Many analysers also count the number of high fluorescence cells (HF cells). HF cells have a large nuclear size and emit high fluorescence when stained with fluorescent dyes. Due to their large nuclear size, Malignant cells are counted as HF cells. We aim to determine the diagnostic utility of HF cells in predicting the presence of malignant cells in serous effusions. HF cell counts were done on 209 serous fluid samples using the body fluid mode of Mindray BC-6800 plus haematology analyser. Papanicilaou-stained smears of all samples were examined for the presence of malignant cells by a panel of cytopathologists. ROC curve analysis was done to determine the sensitivity and specificity of HF cells in malignant effusions. Out of 209 samples, malignant cells were found by microscopy in 97 cases (46.4%). The absolute number and percentage of HF cells were significantly higher (P < 0.001) in malignant effusions (HF# = 24.9 cells/ul, HF% = 10.4%) when compared to non-malignant samples (HF# = 4.95 cells/ul, HF% = 5.76%). ROC curve analysis determined an optimal cut-off of ≥30 HF cells/ul (sensitivity = 73.91, specificity = 55.66%) for the prediction of malignant cells. HF cells in serous effusions can be a helpful tool to aid the pathologist, but it is not an ideal screening test due to its low sensitivity (67.74%) and negative likelihood ratio (0.5) at a cut-off of ≥30 HF cells/ul. However, due to high specificity of 83.18% at a cut-off of ≥72 HF cells/ul, a meticulous search for malignant cells should be done on microscopy.