The Four Color Theorem for Cell Instance Segmentation

Ye Zhang, Yu Zhou, Yifeng Wang, Jun Xiao, Ziyue Wang +2 more
2/14/2026

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Abstract

Cell instance segmentation is critical to analyzing biomedical images, yet accurately distinguishing tightly touching cells remains a persistent challenge. Existing instance segmentation frameworks, including detection-based, contour-based, and distance mapping-based approaches, have made significant progress, but balancing model performance with computational efficiency remains an open problem. In this paper, we propose a novel cell instance segmentation method inspired by the four-color theorem. By conceptualizing cells as countries and tissues as oceans, we introduce a four-color encoding scheme that ensures adjacent instances receive distinct labels. This reformulation transforms instance segmentation into a constrained semantic segmentation problem with only four predicted classes, substantially simplifying the instance differentiation process. To solve the training instability caused by the non-uniqueness of four-color encoding, we design an asymptotic training strategy and encoding transformation method. Extensive experiments on various modes demonstrate our approach achieves state-of-the-art performance. The code is available at https://github.com/zhangye-zoe/FCIS.

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@article{zhang2026four,
  title  = {The Four Color Theorem for Cell Instance Segmentation},
  author = {Ye Zhang and Yu Zhou and Yifeng Wang and Jun Xiao and Ziyue Wang and Yongbing Zhang and Jianxu Chen},
  year   = {2026},
  eprint = {2506.09724},
  archivePrefix = {arXiv},
  url    = {https://arxiv.org/abs/2506.09724},
  journal = {ICML 2025 2025}
}

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