There has been a paradigm shift in the practice of cytopathology with the advent of highly sensitive molecular tests using small amounts of tissue that can provide diagnostic, prognostic, and predictive information for clinical management. The cytopathologist plays a key role in providing a timely and accurate diagnosis as well as ensuring appropriate processing and handling of the specimen and judicious triaging of the tissue for molecular testing that guide therapeutic decisions. As the era of “precision medicine” continues to evolve and expand, cytopathology remains a dynamic field with advances in the practice of molecular cytopathology providing new paradigms in clinical care.