Pathology departments are under significant pressure to meet the demands of a precise medicine environment where general phenotypic attributes are no longer sufficient for accurately defining disease risk, clinical progression and therapeutic options. The classical approach to solid tumor diagnostics combined with immunohistochemical analysis remains the foundation of anatomic pathology; however, recent developments in genomic medicine have altered the paradigm, specifically for lung cancer, colon cancer and melanoma, where DNA mutation detection with next gen sequencing is now part of the pathologist’s tool-box. Although critical for therapeutic selection, there is considerable evidence that DNA analysis is only one part of the ‘precise equation’ as evidenced by the recent success of check-point inhibitors and the importance of in situ immune composition. Furthermore, the field of systems or precise pathology which encompasses digital image analysis and quantitative protein detection integrated with deep learning processes is poised to have a tremendous impact on the practice of pathology in the future. In addition to tissue based analytics the continued advances in the liquid biopsy space including circulating tumor cells, cell-tumor DNA and exosomes combined with serum proteomics will undoubtedly bring another level of complexity to the patient assessment process. With the ever-changing and competitive healthcare atmosphere, novel technologies and data management – bioinformatics will continue to be at the forefront of clinical medicine.