Context. - Diagnostic molecular pathology is rapidly becoming an indispensable tool for anatomic pathologists. Familiarity with some of the technologic principles and current, as well as upcoming, molecular diagnostic applications is greatly advantageous for today's practice of pathology. Objectives. - To provide a discussion of the most common techniques currently used in molecular pathology laboratories and review their essential applications to diagnosis and management of neoplastic diseases. Data Sources. - A literature review and illustrative cases from the authors' molecular diagnostic practices. Conclusions. - Applications such as clonality assays, molecular cytogenetics, and chimerism analysis are providing us with accurate tools to resolve difficult diagnostic and management decisions in hemato-oncology. This should serve as a future model to expand molecular applications into the wider field of solid tumors.