Conventional cytogenetic studies are widely used today to diagnose and manage patients with hematological malignancies. The application of fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes helps to further define molecular subclasses and cytogenetic risk categories for patients with these disorders. Moreover, FISH permits analysis of proliferating (metaphase cells) and non-proliferating (interphase nuclei) cells, and is useful in establishing the percentage of neoplastic cells before and after therapy (minimal residual disease). For patients with myelodysplasia or acute myeloid leukemia, these chromosome techniques are important for accurate diagnosis and classification of disease and to help decide treatment and monitor response to therapy. Conventional cytogenetic studies have been problematic in chronic lymphocytic leukemia because the neoplastic cells divide infrequently. However, interphase FISH studies now permit detection of chromosome anomalies with prognostic significance in chronic lymphocytic leukemia. The World Health Organization recognizes that genetic anomalies are one of the most reliable criteria for classification of malignant lymphomas. New methods to extract individual nuclei from paraffin-embedded tissue are now available which permit the use of interphase FISH to detect important chromosome anomalies in lymphoma.