The rapidly expanding fields of pharmacogenomics and pharmacodiagnostics have presented the pathology laboratories with many challenges and opportunities. As custodians of patient tissues, these laboratories are in the logical position to perform biomolecular testing for proper management of patients. In order to meet these challenges, the pathology laboratories of the twenty-first century should design and execute a biomarker-friendly, standardized tissue handling, including fixation and processing, to ensure uniform protection of macromolecules for clinically useful molecular assays. This important pre-analytic phase cannot be successful if tissues are handled in the traditional manner that includes the use of conventional fixation and processing. The recent progress in fixation and processing methods are rapidly replacing the time-honored routine formalin fixation and overnight processing. In this article we describe our experience with such system that not only produces good histomorphology but also preserves high quality RNA, DNA, and proteins in paraffin embedded material.