<b><i>Introduction:</i></b> The aim of this study is to discover a fast and efficient method for the diagnosis of serous effusion cytology specimens by comparing the cytomorphological features of SurePath (SP) smears and smears prepared by cytospin. After the macroscopic features of the incoming material were recorded, it was divided into 2 for conventional technique (CT) and liquid-based technique. Cytospin was used for CT and SurePath for liquid-based technique in this study. <b><i>Materials and Methods:</i></b> 243 serous effusions (33 thoracentesis and 92 paracentesis fluids, 118 peritoneal lavage fluids) were investigated. After shaking the effusion gently, it was centrifuged for 5 min at 1,250 rpm for cytospin smear. SP smear was prepared according to the “BD PrepStain slide processor”. Two smears were prepared with these 2 methods and then stained with Papanicolaou. The smears were examined under a light microscope in terms of fixation, background, cellularity, nucleus, and structural features. All statistical analysis of the data was performed using the SPSS 17.0 software. For each microscopic feature, the χ<sup>2</sup> test was used to assess the significance of the relationship between cytospin and SP, and level of agreement in between the methods was assessed using the kappa statistic. <b><i>Results:</i></b> A statistically significant difference was observed between the 2 methods in background (<i>p</i> < 0.001), cellularity (<i>p</i> < 0.001), nucleus features (<i>p</i> < 0.001), and structural features (<i>p</i> < 0.05). There was no significant difference in fixation. Low level of agreement was observed with the kappa statistic in fixation, background, and cellularity. Moderate level of agreement was observed in the nucleus and structural feature groups with the kappa statistic. <b><i>Discussion/Conclusion:</i></b> Although there are advantages of liquid-based technique such as standardized fixation and cleaner background, since the cellular and background components required for morphological analysis and diagnosis are better preserved in cytospin, it is considered to be better to use liquid-based technique not alone but together with CT.