Digitally automated spatial profiling of immune-tumor cell interactions using multispectral immunofluorescence shows promise as a biomarker for predicting outcomes in early-stage breast cancer. This approach allows to analyze the topology and proximity between specific populations of cells in the preserved tissue architecture. Prospective validation and harmonization with existing biomarkers is needed before clinical adoption. Authors David B. Page, Michael Simanonok, Douglas A. Hanes, and Alan Su discuss the clinical potential and challenges of this profiling of tumor-infiltrating lymphocytes. The method quantitatively evaluates key tumor-immune pathways. It serves to stratify patients in the initial stage of breast cancer.