Recent advances in molecular biological techniques have contributed to the tremendous progression made in the field of diagnosis of leukemia. Discovery of T- or B-lymphocyte associated genes, tumor specific genes and genes involved in chromosomal translocation has made it possible to detect leukemia cells by Southern blotting, PCR, RT-PCR or fluorescence in situ hybridization (FISH). The recently developed FISH is a simple, rapid and accurate method and requires a very small amount of specimen (about 500-1000 cells). It is possible to obtain results within 48 hours of sampling. This lecture were focused on two topics; 1) The application of FISH method in the diagnosis of leukemia using three types of probes (whole chromosome painting probe, centromeric probes and oncogene specific probes) and their combinations. 2) Clarification of concepts made by molecular biology especially in Philadelphia chromosome positive leukemia, Ph-negative chronic myelocytic leukemia, endemic/sporadic type of Burkitt's lymphoma, biphenotypic leukemia and leukemia with specific translocations.