Difference-Deformable Convolution With Pseudo Scale Instance Map for Cell Localization Cell localization still faces two unresolved challenges: 1) the dramatic variations in cell morphology, coupled with the heterogeneous intensity distribution of lightly stained cells; 2) existing cell location maps lack scale information, resulting in insufficient supervision for point maps and inaccurate supervision for density maps. 1) To address the first challenges, we introduce a novel gradient-aware and shape-adaptive Difference-Deformable Convolution (DDConv), which enhances the model’s ro- bustness to color by leveraging gradient information while adaptively adjusting the shape of the convolutional ker- nel to tackle the substantial variability in cell morphology. 2) To overcome the issue of unreasonable location maps, we propose the Pseudo-Scale Instance (PSI) map, which can adaptively provide the corresponding scale information for each cell to realize accurate supervision. We analyze and evaluate DDConv and the PSI map in three challenging cell localization tasks. In comparison to existing methods, our proposed approach significantly enhances localization performance, setting a new benchmark for the cell localiza- tion task.