Nuclear delineation and phenotypic profiling are important steps in the automated analysis of histology sections. However, these are challenging problems due to (i) technical variations (e.g., fixation, staining) that originate as a result of sample preparation, (ii) biological heterogeneity (e.g., vesicular versus high chromatin phenotypes, nuclear atypia), and (iii) overlapping nuclei. This Application-Note couples contextual information about the cellular organization with the individual signature of nuclei to improve performance. As a result, routine delineation of nuclei in H&E stained histology sections is enabled for either computer-aided pathology (CAP) or integration with genome-wide molecular data.