Objective: The cell block (CB) is an important adjunct to cytological preparations in diagnostic cytopathology. Optimizing cellular material in the CB is essential to the success of ancillary studies such as immunohistochemistry (IHC) and molecular studies (MS). Our aim was to identify which CB method was most suitable in a variety of specimen types and levels of cellularity. Study Design: We assessed 4 different CB methods, thrombin clot method (TCM), MD Anderson method (MDAM), gelatin foam method (GFM), and agar method (AM), with descriptive observations and ranking of the methods based on quantity of cells and morphological features. Results: TCM performed best in ranking for both quantity of cells and morphological features, followed by MDAM, GFM, and AM. Lack of adjuvant in the MDAM resulted in some unique morphological advantages which, however, also resulted in inconsistent performance. In low cellularity cases insufficient cells were frequently identified on slides from MDAM and AM CBs. Technique touch time was similar for all methods, with total processing time being shortest for TCM followed by MDAM, GFM, and AM. Conclusions: TCM was the most robust CB technique, retaining high scores for ranking of quantity and morphology in a variety of specimen cellularities and specimen types.