Over the past decade molecular genetic methods have played an increasingly important role in the diagnosis of hematologic malignancies. Moreover, they have provided a tool to analyze many of the non-random cytogenetic anomalies associated with hematologic neoplasias, contributing considerably to our understanding of several of those diseases, and to improving diagnostic accuracy. The rapid development of molecular genetics progressively allows the replacement of time-consuming and technically demanding procedures. Even more relevant are the new clinical applications that already include the search for valuable prognostic information and ways of evaluating minimal residual disease or recognizing early relapsing disease. This paper is a critical but necessarily simplified overview of the main contributions of molecular genetics to the field of hematopathology. We discuss the information provided by several molecular methods within different clinical contexts, covering common problems in diagnostic pathology as well as prognostic evaluation and therapy monitoring.