Microscopy Cell Segmentation: Review and Benchmarking of Task-Specific and Foundation Models

Cell segmentation plays a key role in a wide range of biomedical imaging applications, from single-cell analysis to pathology assessment. While classical deep learning architectures such as U-Net, StarDist, and HoVer-Net have set strong baselines, their reliance on domain-specific training limits generalization across diverse microscopy modalities. The emergence of foundation models, particularly the Segment Anything Model (SAM) and its derivatives, has introduced a paradigm shift toward more universal and adaptable segmentation frameworks. In this review, we summarize key advances in microscopy cell segmentation, highlighting both traditional methods and recent foundation model-based approaches. Beyond surveying the literature, we present an experimental comparison of four representative models—our proposed YOLO-SAM, along with CellSAM, Cellpose-SAM, and StarDist—tested on both fluorescence and brightfield microscopy spanning diverse cell populations and shapes. Our findings illustrate trade-offs between accuracy, robustness, and adaptability, with foundation-based models showing particular promise for cross-domain performance. By combining a comprehensive review with systematic benchmarking, this work provides practical guidance for researchers and outlines current challenges and future opportunities in developing robust, generalizable cell segmentation methods for microscopy.