Identification of early diagnostic and prognostic biomarkers measurable in liquid biopsies remains a major challenge in oncology today. OMICs technologies cannot be applied on clinically precious human material as this is required in its integrity for routine pathology investigation. Hence all OMICs discovery today is done on residual and not clinically relevant material. In the study, we present a novel, non-destructive, procedure named EXPEL, which uses rapid, pressure-assisted, interstitial fluid extrusion, allowing for full clinical pathology and OMICs analysis (proteins, metabolites, miRNA and DNA) on the same specimen. To demonstrate this we engage in a simultaneous biomarker discovery and routine diagnostic analysis of human colorectal cancer and liver metastases. Biomarkers discovered with EXPEL methodology can be readily detected in human sera, allowing for unprecedented translation to the clinic. EXPEL method enables for the first time both clinicians and scientist to explore identical, fresh, clinical material regardless of origin and size.